Journal articles on the topic 'KCA'
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1
Rabasseda, X., N. Mealy, and J. Castañer. "KCA-098." Drugs of the Future 20, no. 3 (1995): 235. http://dx.doi.org/10.1358/dof.1995.020.03.288772.
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Li, Anlong, Adebowale Adebiyi, Charles W. Leffler, and Jonathan H. Jaggar. "KCa channel insensitivity to Ca2+ sparks underlies fractional uncoupling in newborn cerebral artery smooth muscle cells." American Journal of Physiology-Heart and Circulatory Physiology 291, no. 3 (September 2006): H1118—H1125. http://dx.doi.org/10.1152/ajpheart.01308.2005.
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In smooth muscle cells, localized intracellular Ca2+ transients, termed “Ca2+ sparks,” activate several large-conductance Ca2+-activated K+ (KCa) channels, resulting in a transient KCa current. In some smooth muscle cell types, a significant proportion of Ca2+ sparks do not activate KCa channels. The goal of this study was to explore mechanisms that underlie fractional Ca2+ spark-KCa channel coupling. We investigated whether membrane depolarization or ryanodine-sensitive Ca2+ release (RyR) channel activation modulates coupling in newborn (1- to 3-day-old) porcine cerebral artery myocytes. At steady membrane potentials of −40, 0, and +40 mV, mean transient KCa current frequency was ∼0.18, 0.43, and 0.26 Hz and KCa channel activity [number of KCa channels activated by Ca2+ sparks × open probability of KCa channels at peak of Ca2+ sparks ( NPo)] at the transient KCa current peak was ∼4, 12, and 24, respectively. Depolarization between −40 and +40 mV increased KCa channel sensitivity to Ca2+ sparks and elevated the percentage of Ca2+ sparks that activated a transient KCa current from 59 to 86%. In a Ca2+-free bath solution or in diltiazem, a voltage-dependent Ca2+ channel blocker, steady membrane depolarization between −40 and +40 mV increased transient KCa current frequency up to ∼1.6-fold. In contrast, caffeine (10 μM), an RyR channel activator, increased mean transient KCa current frequency but did not alter Ca2+ spark-KCa channel coupling. These data indicate that coupling is increased by mechanisms that elevate KCa channel sensitivity to Ca2+ sparks, but not by RyR channel activation. Overall, KCa channel insensitivity to Ca2+ sparks is a prominent factor underlying fractional Ca2+ spark uncoupling in newborn cerebral artery myocytes.
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Zhang, Xiaolei, Meitao Yang, Dan Lv, Yin Xie, Yanan Sun, Yanling Zhang, Mengzhou He, Haiyi Liu, Fanfan Li, and Dongrui Deng. "Effects of KCa channels on biological behavior of trophoblasts." Open Life Sciences 17, no. 1 (January 1, 2022): 1043–52. http://dx.doi.org/10.1515/biol-2022-0462.
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Abstract The Ca2+-activated potassium (KCa) channels are involved in many cellular functions, but their roles in trophoblasts are unclear. This study aimed to clarify the effects of KCa channels on the biological behavior of trophoblasts. The localization and expression of the three types of KCa channels, including large-conductance KCa channels (BKCa), intermediate-conductance KCa channels (IKCa), and small-conductance KCa channels (SKCa), were detected in human chorionic villi taken from pregnant women between 5 and 8 weeks of gestation (n = 15) and HTR-8/SVneo cells. The effects of KCa channels on proliferation, apoptosis, and migration of HTR-8/SVneo cells were examined by using the activators or inhibitors of KCa channels. Results showed that KCa channels were mainly localized on the membrane and in the cytoplasm of trophoblasts in human chorionic villi and HTR-8/SVneo cells. The proliferation and migration of HTR-8/SVneo cells were inhibited by activating KCa channels. Apoptosis of trophoblasts was promoted through activating BKCa channels but was not affected by neither activating nor inhibiting IKCa and SKCa channels. This study substantiated the abovementioned biological roles of KCa channels in trophoblast cells, which is fundamental to further research on whether dysfunction of KCa channels is involved in the pathogenesis of pregnancy-related complications.
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Wang, Rui, and Lingyun Wu. "Interaction of Selective Amino Acid Residues of KCa Channels with Carbon Monoxide." Experimental Biology and Medicine 228, no. 5 (May 2003): 474–80. http://dx.doi.org/10.1177/15353702-0322805-09.
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The activation of big-conductance KCa channels in vascular smooth muscle cells by carbon monoxide (CO) has been demonstrated previously. One specific target of CO on KCa channel proteins is the histidine residue. The roles of other amino acid residues on the functionality of KCa channels, as well as their reactions to CO, have been unclear. In the present study, the cell-free single channel recording technique was used to investigate the chemical modification of KCa channels by CO and other chemical agents. The modification of negatively charged carboxyl groups and the ε-amino group of lysine did not affect the open probability, but decreased single-channel conductance of KCa channels. When sulfhydryl groups of cysteine were modified with N-ethylmaleimide, the open probability of KCa channels was decreased, but single-channel conductance was not affected. None of the above chemical modifications affected the CO-induced increase in the open probability of KCa channels. However, N-ethylmaleimide treatment reduced the stimulatory effect of nitric oxide (NO) on KCa channels. Finally, pretreatment of smooth muscle cells with NO abolished the effects of subsequently applied CO on KCa channel proteins. Our study demonstrates that CO and NO acted on different amino acid residues of KCa channel proteins. The interaction of CO and NO determines the functional status of KCa channels in vascular smooth muscle cells
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Zhao, Guiling, Adebowale Adebiyi, Qi Xi, and Jonathan H. Jaggar. "Hypoxia reduces KCa channel activity by inducing Ca2+ spark uncoupling in cerebral artery smooth muscle cells." American Journal of Physiology-Cell Physiology 292, no. 6 (June 2007): C2122—C2128. http://dx.doi.org/10.1152/ajpcell.00629.2006.
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Arterial smooth muscle cell large-conductance Ca2+-activated potassium (KCa) channels have been implicated in modulating hypoxic dilation of systemic arteries, although this is controversial. KCa channel activity in arterial smooth muscle cells is controlled by localized intracellular Ca2+ transients, termed Ca2+ sparks, but hypoxic regulation of Ca2+ sparks and KCa channel activation by Ca2+ sparks has not been investigated. We report here that in voltage-clamped (−40 mV) cerebral artery smooth muscle cells, a reduction in dissolved O2 partial pressure from 150 to 15 mmHg reversibly decreased Ca2+ spark-induced transient KCa current frequency and amplitude to 61% and 76% of control, respectively. In contrast, hypoxia did not alter Ca2+ spark frequency, amplitude, global intracellular Ca2+ concentration, or sarcoplasmic reticulum Ca2+ load. Hypoxia reduced transient KCa current frequency by decreasing the percentage of Ca2+ sparks that activated a transient KCa current from 89% to 63%. Hypoxia reduced transient KCa current amplitude by attenuating the amplitude relationship between Ca2+ sparks that remained coupled and the evoked transient KCa currents. Consistent with these data, in inside-out patches at −40 mV hypoxia reduced KCa channel apparent Ca2+ sensitivity and increased the Kd for Ca2+ from ∼17 to 32 μM, but did not alter single-channel amplitude. In summary, data indicate that hypoxia reduces KCa channel apparent Ca2+ sensitivity via a mechanism that is independent of cytosolic signaling messengers, and this leads to uncoupling of KCa channels from Ca2+ sparks. Transient KCa current inhibition due to uncoupling would oppose hypoxic cerebrovascular dilation.
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Cheng, Xiaoyang, and Jonathan H. Jaggar. "Genetic ablation of caveolin-1 modifies Ca2+ spark coupling in murine arterial smooth muscle cells." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 6 (June 2006): H2309—H2319. http://dx.doi.org/10.1152/ajpheart.01226.2005.
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L-type, voltage-dependent calcium (Ca2+) channels, ryanodine-sensitive Ca2+ release (RyR) channels, and large-conductance Ca2+-activated potassium (KCa) channels comprise a functional unit that regulates smooth muscle contractility. Here, we investigated whether genetic ablation of caveolin-1 (cav-1), a caveolae protein, alters Ca2+ spark to KCa channel coupling and Ca2+ spark regulation by voltage-dependent Ca2+ channels in murine cerebral artery smooth muscle cells. Caveolae were abundant in the sarcolemma of control (cav-1+/+) cells but were not observed in cav-1-deficient (cav-1−/−) cells. Ca2+ spark and transient KCa current frequency were approximately twofold higher in cav-1−/− than in cav-1+/+ cells. Although voltage-dependent Ca2+ current density was similar in cav-1+/+ and cav-1−/− cells, diltiazem and Cd2+, voltage-dependent Ca2+ channel blockers, reduced transient KCa current frequency to ∼55% of control in cav-1+/+ cells but did not alter transient KCa current frequency in cav-1−/− cells. Furthermore, although KCa channel density was elevated in cav-1−/− cells, transient KCa current amplitude was similar to that in cav-1+/+ cells. Higher Ca2+ spark frequency in cav-1−/− cells was not due to elevated intracellular Ca2+ concentration, sarcoplasmic reticulum Ca2+ load, or nitric oxide synthase activity. Similarly, Ca2+ spark amplitude and spread, the percentage of Ca2+ sparks that activated a transient KCa current, the amplitude relationship between sparks and transient KCa currents, and KCa channel conductance and apparent Ca2+ sensitivity were similar in cav-1+/+ and cav-1−/− cells. In summary, cav-1 ablation elevates Ca2+ spark and transient KCa current frequency, attenuates the coupling relationship between voltage-dependent Ca2+ channels and RyR channels that generate Ca2+ sparks, and elevates KCa channel density but does not alter transient KCa current activation by Ca2+ sparks. These findings indicate that cav-1 is required for physiological Ca2+ spark and transient KCa current regulation in cerebral artery smooth muscle cells.
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Van Hemelrijck, M., H. Garmo, N. Hammar, G. Walldius, M. Lambe, I. Jungner, and L. Holmberg. "Lipid profiles and the risk of kidney cancer in the Swedish AMORIS study." Journal of Clinical Oncology 29, no. 7_suppl (March 1, 2011): 342. http://dx.doi.org/10.1200/jco.2011.29.7_suppl.342.
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342 Background: Since multiple epidemiologic studies showed a link between obesity and kidney cancer (KCa), the lipid metabolism is thought to play a role in development of KCa. With the exception of cholesterol and total fat intake, the association between changes in lipid biomarkers and KCa has not often been researched. We assessed the link between lipid profiles and KCa risk in a large prospective cohort study. Methods: A cohort based on 85,261 persons (> 20 years old) with baseline measurements of glucose, triglycerides (TG), total cholesterol, HDL, LDL, apolipoprotein A-I and apoB was selected from the Swedish Apolipoprotein Mortality Risk (AMORIS) study. Multivariate Cox proportional hazards models were used to analyze associations between quartiles and dichotomized values of these lipid components and KCa risk. All models were adjusted for age, gender, socioeconomic status, fasting status, history of kidney disease prior to baseline (ICD9: 580-93), and glucose, cholesterol, and TG levels (depending on the covariate of interest). Results: During a mean follow-up of 12 years, 161 persons developed KCa (58% men). The mean age at baseline was 46 years. TG were the only lipid component for which a statistically significant association was found with risk of KCa (Hazard Ratio (HR): 1.05 (95%CI: 0.59-1.87), 1.77 (1.05-2.98), and 1.77 (1.04-3.02) for the second, third, and fourth quartile, compared to the first, with p-value for trend: 0.008). The lipid ratio of TG and HDL also showed a statistically significant positive association with risk of KCa (HR: 1.21 (0.71-2.08), 1.56 (0.94-2.58), and 1.92 (1.17-3.17) for the second, third, and fourth quartile, compared to the first, with p-value for trend: 0.004). No other associations were found between lipid components and KCa risk. Conclusions: This detailed analysis of lipid components and risk of KCa found a relation between levels of TG and KCa risk. In contrast to previous studies, we did not find an association between cholesterol levels and KCa risk. Lipid profiles based on the markers used in this study do not seem to reflect the etiological pathway that has previously been shown between obesity and KCa. Further mechanistic studies are required to assess the link between lipid deregulation and KCa. No significant financial relationships to disclose.
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Orfali, Razan, Ali AlFaiz, Mohammad Asikur Rahman, Liz Lau, Young-Woo Nam, and Miao Zhang. "KCa2 and KCa3.1 Channels in the Airways: A New Therapeutic Target." Biomedicines 11, no. 7 (June 21, 2023): 1780. http://dx.doi.org/10.3390/biomedicines11071780.
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K+ channels are involved in many critical functions in lung physiology. Recently, the family of Ca2+-activated K+ channels (KCa) has received more attention, and a massive amount of effort has been devoted to developing selective medications targeting these channels. Within the family of KCa channels, three small-conductance Ca2+-activated K+ (KCa2) channel subtypes, together with the intermediate-conductance KCa3.1 channel, are voltage-independent K+ channels, and they mediate Ca2+-induced membrane hyperpolarization. Many KCa2 channel members are involved in crucial roles in physiological and pathological systems throughout the body. In this article, different subtypes of KCa2 and KCa3.1 channels and their functions in respiratory diseases are discussed. Additionally, the pharmacology of the KCa2 and KCa3.1 channels and the link between these channels and respiratory ciliary regulations will be explained in more detail. In the future, specific modulators for small or intermediate Ca2+-activated K+ channels may offer a unique therapeutic opportunity to treat muco-obstructive lung diseases.
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Yang, Yuqin, Jan van Aalst, and Carol Chan. "Examining Online Discourse Using the Knowledge Connection Analyzer Framework and Collaborative Tools in Knowledge Building." Sustainability 13, no. 14 (July 19, 2021): 8045. http://dx.doi.org/10.3390/su13148045.
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This study examines the problem of the fragmentation of asynchronous online discourse by using the Knowledge Connection Analyzer (KCA) framework and tools and explores how students could use the KCA data in classroom reflections to deepen their knowledge building (KB) inquiry. We applied the KCA to nine Knowledge Forum® (KF) databases to examine the framework, identify issues with online discourse that may inform further development, and provide data on how the tools work. Our comparisons of the KCA data showed that the databases with more sophisticated teacher–researcher co-design had higher KCA indices than those with regular KF use, validating the framework. Analysis of KF discourse using the KCA helped identify several issues including limited collaboration among peers, underdeveloped practices of synthesizing and rising above of collective ideas, less analysis of conceptual development of discussion threads, and limited collaborative reflection on individual contribution and promising inquiry direction. These issues that open opportunities for further development cannot be identified by other present analytics tools. The exploratory use of the KCA in real classroom revealed that the KCA can support students’ productive reflective assessment and KB. This study discusses the implications for examining and scaffolding online discussions using the KCA assessment framework, with a focus on collective perspectives regarding community knowledge, synthesis, idea improvement, and contribution to community understanding.
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Sukiman, Sukiman. "Studi Komparatif Pendapatan Produk Kredit Cepat Aman (Kca) Dengan Produk Kredit Angsuran Sistem Fidusia (Kreasi) Di Pt. Pegadaian Cabang Sinjai (Analisis Tinjauan Syariah)." Jurnal Asy-Syarikah: Jurnal Lembaga Keuangan, Ekonomi dan Bisnis Islam 1, no. 1 (October 30, 2019): 40–63. http://dx.doi.org/10.47435/asy-syarikah.v1i1.86.
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Penelitian ini bertujuan untuk mengetahui perbandingan pendapatan Pegadaian yang peroleh dari produk Kredit Cepat Aman (KCA) dengan produk Kredit Angsuran Sistem Fidusia (KREASI) di PT. Pegadaian Cabang Sinjai dan tinjauan syariah terhadap pendapatan produk Kredit Cepat Aman (KCA)dan produk Sistem Fidusia (KREASI). Penelitian ini termasuk jenis penelitian kuantitatif dengan menggunakan pendekatan analisis komparatif. Penelitian ini merupakan penelitian yang menggunakan nasabah produk Kredit Cepat Aman (KCA) dengan produk Kredit Angsuran Sistem Fidusia (KREASI) di PT. Pegadaian Cabang Sinjai sebagai objek penelitian. Data penelitian diperoleh melalui dokumentasi dengan menggunakan instrumen pedoman dokumentasi. Data yang diperoleh dianalisis dengan uji z dan analisis kualitatif. Hasil penelitian menunjukkan bahwa: (1) Pendapatan Pegadaian yang diperoleh dari produk KCA dan KREASI adalah Rp.15.723.800 dan Rp.35.835.000 dengan jumlah pendapatan yang diperoleh produk KREASI lebih besar Rp.20.111.200 dari pada produk KCA. Adapun rata-rata pendapatan produk KCA Rp.524.127 dan KREASI Rp.1.194.500 dan berdasarkan hasil uji hipotesis dengan menggunakan uji Z menunjukkan nilai Z Tabel 0,999999997>0,05, oleh karena itu perbandingan rata-rata pendapatan produk KCA dan KREASI di PT. Pegadaian Cabang Sinjai signifikan. (2) Pendapatan Pegadaian pada produk KCA dan KREASI yang diperoleh dari penarikan sewa modal atau bunga kepada nasabah mengandung ungsur riba, karena adanya penambahan jumlah uang yang harus dibayar nasabah dari pinjaman pokok. Dimana setiap bunga 1% dari masing-masing pinjaman nasabah KCA yang harus dibayar adalah Rp.47.949 dan setiap bunga 1% dari masing-masing pinjaman nasabah KREASI yang harus dibayar adalah Rp.115.400 dengan tarif bunga untuk 30 nasabah KCA dan KREASI adalah sebesar Rp.15.723.800 dan Rp.35.835.000. Hal ini bertentangan dengan ayat-ayat dalam Al-Qur’an dan pendapat para ulama yang melarang adanya riba dalam melakukan transaksi, oleh karena itu pendapatan Pegadaian yang diperoleh dari produk KCA dan KREASI merupakan sesuatu yang dilarang dalam Islam dan hukumnya adalah haram.
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Sudiyarti, Nining, Bagas Irwansyah, and Rosyidah Rachman. "PENGARUH KREDIT CEPAT AMAN (KCA) TERHADAP PENDAPATAN NASABAH (Studi Pada Nasabah KCA PT. Pegadaian Cabang Moyo Hilir)." Jurnal Ekonomi & Bisnis 10, no. 3 (December 31, 2022): 284–92. http://dx.doi.org/10.58406/jeb.v10i3.1039.
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This study aims to determine the effect of fast and secure credit (KCA) on the income of customers of PT. Moyo Hilir Service Unit Pegadaian. This type of research is associative research to determine the influence or relationship between two or more variables. The variables that will be studied in this study are fast and secure credit Loans (KCA) as the independent variable (free), and Customer Income as the dependent variable (tied). This study uses quantitative data types obtained from primary sources, namely all fast and secure credit (KCA) customers at PT. Pegadaian Service Unit Moyo Hilir January-June 2022 totaling 51 people. Data collection was carried out using a questionnaire distributed to respondents. The data that has been collected is processed with the help of the SPSS program and studied using simple linear regression analysis techniques, partial parameter hypothesis testing (t test), and determination coefficient test (R2). The results of this study indicate that the granting of fast and secure credit (KCA) has a positive and significant effect on the income of PT. Moyo Hilir Service Unit Pegadaian. The variable ability of granting fast safe credit (KCA) in explaining variations in changes in customer income variables of PT. Pegadaian Service Unit of Moyo Hilir is 80.7%, while the remaining 19.3% is influenced by other variables outside this research model.
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Chun, Sung Su, Timur R. Tadjiev, Kyo Han Kim, J. H. Lee, and Suk Young Kim. "Biodegradation and Characterization of Phase Separated NaCa(PO3)3 and KCa(PO3)3 from Pure Ca(PO3)2." Key Engineering Materials 309-311 (May 2006): 211–14. http://dx.doi.org/10.4028/www.scientific.net/kem.309-311.211.
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Degradation characteristics of calcium metaphosphate (CMP) ceramics substituted by 5, 10, 15, 20 mol% of NaPO3 and KPO3, respectively, was evaluated in revised simulated body fluid (R-SBF) by measuring the weight change, flexural strength, crystalline phases, and surface morphology with immersion period. The weight loss of CMP substituted by KPO3 was significantly higher than that of CMP substituted by NaPO3. The weight loss in the KCa(PO3)3–CMP samples was due to the dissolution of KCa(PO3)3 phase. The flexural strength of NaCa(PO3)3–CMP samples increased, however, that of KCa(PO3)3–CMP samples decreased significantly due to the dissolution of KCa(PO3) phase with immersion period. The dissolution of KCa(PO3)3 phase formed a pore structure in KCa(PO3)3–CMP samples.
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Toro, L., L. Vaca, and E. Stefani. "Calcium-activated potassium channels from coronary smooth muscle reconstituted in lipid bilayers." American Journal of Physiology-Heart and Circulatory Physiology 260, no. 6 (June 1, 1991): H1779—H1789. http://dx.doi.org/10.1152/ajpheart.1991.260.6.h1779.
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This work is the initial characterization of Ca(2+)-activated K+ (KCa) channels from coronary smooth muscle reconstituted into lipid bilayers. The channels were obtained from a surface membrane preparation of porcine coronary smooth muscle. KCa channels were the predominant K+ channels in this preparation. The conductance histogram (n = 137 channels) revealed two main populations of “maxi” KCa channels with conductances of 245 and 295 pS. Each population could be subdivided in two “isoforms” or “isochannels” with different functional properties (voltage and Ca2+ sensitivities and kinetics). The analysis of “burst” probability of opening showed that at pCa 4 the two isochannels of 245 pS (KCa-1 and KCa-1') had half-activation potentials (V1/2) of -80 and 6 mV, respectively. The isochannels of 295 pS (KCa-2 and KCa-2') had V1/2 of -28 and -66 mV, respectively. KCa-1 had the highest Ca2+ sensitivity; at -60 mV, the concentration of half-activation value for Ca2+ was 1.2 +/- 0.3 microM (n = 5). External tetraethylammonium reduced channel amplitude in a voltage-dependent manner; dissociation constant was 180 +/- 6 and 466 +/- 41 microM at -40 and +80 mV, respectively (n = 5). Charybdotoxin (5-50 nM) produced typical long closings. These effects were similar in all the channels. We conclude that coronary smooth muscle possesses isoforms of maxi KCa channels with Ca2+ and voltage sensors with different properties, which may confer to each channel a specific functional role.
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Maruiwa, M., A. Mizoguchi, G. J. Russell, N. Narula, M. Stronska, E. Mizoguchi, H. Rabb, M. A. Arnaout, and A. K. Bhan. "Anti-KCA-3, a monoclonal antibody reactive with a rat complement C3 receptor, distinguishes Kupffer cells from other macrophages." Journal of Immunology 150, no. 9 (May 1, 1993): 4019–30. http://dx.doi.org/10.4049/jimmunol.150.9.4019.
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Abstract A new mAb, designated anti-KCA-3, was developed against rat Kupffer cells. The reactivity of anti-KCA-3 was restricted to macrophages with preferential binding to Kupffer cells; only a few macrophages in the spleen, lymph nodes, lungs, and intestine stained with the antibody. A very small number of peritoneal resident and exudate macrophages reacted with the antibody and no reactivity was seen within the thymus, skin, heart, kidneys, brain, peripheral blood, and bone marrow. KCA-3 was expressed predominantly by the Kupffer cells in the periportal region rather than in the centrilobular region of the hepatic lobules. The cells in the portal tract did not stain with the antibody. The staining of the cytosmears and FACS analysis of the Kupffer cell fraction isolated from hepatic sinusoidal cells by centrifugal elutriation revealed that as many as 62% and 49% of the cells were stained with anti-KCA-3, respectively. Immunoelectron microscopic study of the liver indicated that expression of KCA-3 on Kupffer cells was limited to the plasma membrane facing the sinusoid rather than the space of Disse. Immunoprecipitation and SDS-PAGE analysis demonstrated KCA-3 to have a m.w. of approximately 50 kDa under both reducing and nonreducing conditions. After treatment of KCA-3 with N-glycanase, there was no significant change in the m.w., indicating KCA-3 was not highly glycosylated. C3b- and iC3b-mediated rosette formation between Kupffer cells and sensitized SRBC was inhibited by the antibody, implying that KCA-3 functioned as a complement C3 receptor or complement receptor-associated molecule. Furthermore, KCA-3 was eluted from C3b-Sepharose but not HSA-Sepharose after incubation with Kupffer cell lysate, indicating that KCA-3 directly binds C3b. The cell distribution, ligand-binding specificity, and biochemical properties of the protein were found to be different from the complement C3 receptors previously described. Because OX42 (antibody reactive with the rat CR3 receptor) inhibited complement C3-mediated rosette formation with peritoneal resident macrophages but not with Kupffer cells, the findings suggest that C3-mediated binding to Kupffer cells and to peritoneal macrophages is mediated by two different receptors. We conclude that anti-KCA-3 recognizes a novel type of complement C3 receptor preferentially expressed on Kupffer cells.
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Han, Jin, Nari Kim, Hyun Joo, and Euiyong Kim. "Ketamine blocks Ca2+-activated K+ channels in rabbit cerebral arterial smooth muscle cells." American Journal of Physiology-Heart and Circulatory Physiology 285, no. 3 (September 2003): H1347—H1355. http://dx.doi.org/10.1152/ajpheart.00194.2003.
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Although ketamine and Ca2+-activated K+ (KCa) channels have been implicated in the contractile activity regulation of cerebral arteries, no studies have addressed the specific interactions between ketamine and the KCa channels in cerebral arteries. The purpose of this study was to examine the direct effects of ketamine on KCa channel activities using the patch-clamp technique in single-cell preparations of rabbit middle cerebral arterial smooth muscle. We tested the hypothesis that ketamine modulates the KCa channel activity of the cerebral arterial smooth muscle cells of the rabbit. Vascular myocytes were isolated from rabbit middle cerebral arteries using enzymatic dissociation. Single KCa channel activities of smooth muscle cells from rabbit cerebral arteries were recorded using the patch-clamp technique. In the inside-out patches, ketamine in the micromolar range inhibited channel activity with a half-maximal inhibition of the ketamine conentration value of 83.8 ± 12.9 μM. The Hill coefficient was 1.2 ± 0.3. The slope conductance of the current-voltage relationship was 320.1 ± 2.0 pS between 0 and +60 mV in the presence of ketamine and symmetrical 145 mM K+. Ketamine had little effect on either the voltage-dependency or open- and closed-time histograms of KCa channel. The present study clearly demonstrates that ketamine inhibits KCa channel activities in rabbit middle cerebral arterial smooth muscle cells. This inhibition of KCa channels may represent a mechanism for ketamine-induced cerebral vasoconstriction.
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Setyaningsih, Fety, Eni Indriani, and Nungki Kartikasari. "PENGARUH PENDAPATAN, HARGA EMAS, DAN JUMLAH NASABAH TERHADAP PEMBIAYAAN KREDIT CEPAT AMAN (KCA) PT. PEGADAIAN CABANG KOPANG, LOMBOK TENGAH PADA MASA PANDEMI COVID-19." Jurnal Riset Mahasiswa Akuntansi 3, no. 1 (March 17, 2023): 54–67. http://dx.doi.org/10.29303/risma.v3i1.386.
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Penelitian ini bertujuan untuk menguji pengaruh pendapatan, harga emas, dan jumlah nasabah terhadap pembiayaan Kredit Cepat Aman (KCA) PT. Pegadaian Cabang Kopang, Lombok Tengah pada masa pandemi COVID-19. Jenis penelitian yang digunakan adalah penelitian asosiatif dengan pendekatan kuantitatif. Penelitian ini menggunakan data sekunder berupa data pendapatan PT. Pegadaian Cabang Kopang, harga emas, jumlah nasabah, dan penyaluran KCA pada masa pandemi COVID-19 pada periode 9 Maret 2020-31 Desember 2021. Teknik analisis data yang digunakan berupa uji statistik deskriptif, uji asumsi klasik, dan analisis regresi linear berganda dengan bantuan SPSS 25. Hasil penelitian menunjukkan bahwa pendapatan berpengaruh negatif terhadap pembiayaan KCA. Harga emas berpengaruh positif terhadap pembiayaan KCA. Jumlah nasabah berpengaruh positif terhadap pembiayaan KCA.
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Cornfield, David N., Ernesto R. Resnik, Jean M. Herron, and Steven H. Abman. "Chronic intrauterine pulmonary hypertension decreases calcium-sensitive potassium channel mRNA expression." American Journal of Physiology-Lung Cellular and Molecular Physiology 279, no. 5 (November 1, 2000): L857—L862. http://dx.doi.org/10.1152/ajplung.2000.279.5.l857.
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Calcium-sensitive potassium (KCa) channels play a critical role in mediating perinatal pulmonary vasodilation. Because infants with persistent pulmonary hypertension of the newborn (PPHN) have blunted vasodilator responses to birth-related stimuli, we hypothesized that lung KCachannel gene expression is decreased in PPHN. To test this hypothesis, we measured KCa channel gene expression in distal lung homogenates from both fetal lambs with severe pulmonary hypertension caused by prolonged compression of the ductus arteriosus and age-matched, sham-operated animals (controls). After at least 9 days of compression of the ductus arteriosus, fetal lambs were killed. To determine lung KCa channel mRNA levels, primers were designed against the known sequence of the KCa channel and used in semiquantitative RT-PCR, with lung 18S rRNA content as an internal control. Compared to that in control lambs, lung KCa channel mRNA content in the PPHN group was reduced by 26 ± 6% ( P < 0.02), whereas lung voltage-gated K+ 2.1 mRNA content was unchanged. We conclude that lung KCa channel mRNA expression is decreased in an ovine model of PPHN. Decreased KCa channel gene expression may contribute to the abnormal pulmonary vascular reactivity associated with PPHN.
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Cameron, Jill S., and Stuart E. Dryer. "BK-Type KCa Channels in Two Parasympathetic Cell Types: Differences in Kinetic Properties and Developmental Expression." Journal of Neurophysiology 84, no. 6 (December 1, 2000): 2767–76. http://dx.doi.org/10.1152/jn.2000.84.6.2767.
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The intrinsic electrical properties of identified choroid and ciliary neurons of the chick ciliary ganglion were examined by patch-clamp recording methods. These neurons are derived from a common pool of mesencephalic neural crest precursor cells but innervate different target tissues and have markedly different action potential waveforms and intrinsic patterns of repetitive spike discharge. Therefore it is important to determine whether these cell types express different types of plasma membrane ionic channels, and to ascertain the developmental stages at which these cell types begin to diverge. This study has focused on large-conductance Ca2+-activated K+ channels (KCa), which are known to regulate spike waveform and repetitive firing in many cell types. Both ciliary ganglion cell types, identified on the basis of size and somatostatin immunoreactivity, express a robust macroscopic KCa carried by a kinetically homogeneous population of large-conductance (BK-type) KCachannels. However, the kinetic properties of these channels are different in the two cell types. Steady-state fluctuation analyses of macroscopic KCa produced power spectra that could be fitted with a single Lorentzian curve in both cell types. However, the resulting corner frequency was significantly lower in choroid neurons than in ciliary neurons, suggesting that the underlying KCa channels have a longer mean open-time in choroid neurons. Consistent with fluctuation analyses, significantly slower gating of KCa channels in choroid neurons was also observed during macroscopic activation and deactivation at membrane potentials positive to −30 mV. Differences in the kinetic properties of KCa channels could also be observed directly in single-channel recordings from identified embryonic day 13 choroid and ciliary neurons. The mean open-time of large-conductance KCa channels was significantly greater in choroid neurons than in ciliary neurons in excised inside-out patches. The developmental expression of functional KCa channels appears to be regulated differently in the two cell types. Although both cell types acquire functional KCa at the same developmental stages ( embryonic days 9–13), functional expression of these channels in ciliary neurons requires target-derived trophic factors. In contrast, expression of functional KCa channels proceeds normally in choroid neurons developing in vitro in the absence of target-derived trophic factors. Consistent with this, extracts of ciliary neuron target tissues (striated muscle of the iris/ciliary body) contain KCa stimulatory activity. However, KCa stimulatory activity cannot be detected in extracts of the smooth muscle targets of choroid neurons.
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Egan, T. M., D. Dagan, and I. B. Levitan. "Properties and modulation of a calcium-activated potassium channel in rat olfactory bulb neurons." Journal of Neurophysiology 69, no. 5 (May 1, 1993): 1433–42. http://dx.doi.org/10.1152/jn.1993.69.5.1433.
Full textAbstract:
1. Single calcium-activated potassium channels (KCa channels) were recorded from membrane patches of rat olfactory bulb neurons in culture. Only one kind of KCa channel was seen, and it was present in approximately 50% of detached patches. 2. This channel, like maxi-KCa channels of other tissues, had a single-channel conductance of 270 pS, a reversal potential (Erev) of 0 mV in symmetrical K+, and was highly selective for K+ over Na+ and Cl-. 3. The KCa channel was blocked by d-tubocurarine (d-TC) on the cytoplasmic side, and charybdotoxin (CTX) on the extracellular side. This pharmacology is identical to that of one type of KCa channel from rat brain, observed previously in artificial bilayers and called the type 1 KCa channel. 4. The probability that the channel was in the open state (Po) increased with membrane depolarization. The position of the Po versus transmembrane voltage (Vm) curve was shifted by changes in [Ca2+]i so that the channel was open more often in higher [Ca2+]i. The gating kinetics resembled those of the type 1 KCa channel observed in bilayers. 5. Po was increased after superfusion of the cytoplasmic membrane surface with the active catalytic subunit of cyclic AMP-dependent protein kinase (PK-A), together with MgATP. Phosphorylation altered the distribution of channel closed times but had little effect on open times. The results suggest that phosphorylation is an important molecular mechanism in modulating the activity of this KCa channel from mammalian brain.
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Schubert, Rudolf, Thomas Noack, and Vladimir N. Serebryakov. "Protein kinase C reduces the KCa current of rat tail artery smooth muscle cells." American Journal of Physiology-Cell Physiology 276, no. 3 (March 1, 1999): C648—C658. http://dx.doi.org/10.1152/ajpcell.1999.276.3.c648.
Full textAbstract:
The hypothesis that protein kinase C (PKC) is able to regulate the whole cell Ca-activated K (KCa) current independently of PKC effects on local Ca release events was tested using the patch-clamp technique and freshly isolated rat tail artery smooth muscle cells dialyzed with a strongly buffered low-Ca solution. The active diacylglycerol analog 1,2-dioctanoyl- sn-glycerol (DOG) at 10 μM attenuated the current-voltage ( I- V) relationship of the KCa current significantly and reduced the KCacurrent at +70 mV by 70 ± 4% ( n = 14). In contrast, 10 μM DOG after pretreatment of the cells with 1 μM calphostin C or 1 μM PKC inhibitor peptide, selective PKC inhibitors, and 10 μM 1,3-dioctanoyl- sn-glycerol, an inactive diacylglycerol analog, did not significantly alter the KCa current. Furthermore, the catalytic subunit of PKC (PKCC) at 0.1 U/ml attenuated the I- Vrelationship of the KCa current significantly, reduced the KCacurrent at +70 mV by 44 ± 3% ( n = 17), and inhibited the activity of single KCa channels at 0 mV by 79 ± 9% ( n = 6). In contrast, 0.1 U/ml heat-inactivated PKCC did not significantly alter the KCacurrent or the activity of single KCa channels. Thus these results suggest that PKC is able to considerably attenuate the KCa current of freshly isolated rat tail artery smooth muscle cells independently of effects of PKC on local Ca release events, most likely by a direct effect on the KCa channel.
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Peng, W., J. R. Hoidal, and I. S. Farrukh. "Regulation of Ca(2+)-activated K+ channels in pulmonary vascular smooth muscle cells: role of nitric oxide." Journal of Applied Physiology 81, no. 3 (September 1, 1996): 1264–72. http://dx.doi.org/10.1152/jappl.1996.81.3.1264.
Full textAbstract:
Nitric oxide (NO.) is believed to mediate nitrovasodilators and acetylcholine-induced vasodilatation via increasing intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels. The cellular mechanisms involved in No.-mediated pulmonary vasodilatation are complex and include membrane hyperpolarization. Using the patch-clamp technique in cell-attached and inside-out configurations, we examined the effect of NO. gas, 3-morpholinosydnomimine hydrochloride (SIN-1), and perfusate from ACh-stimulated human pulmonary arterial endothelial cells, or endothelium-derived relaxing factors (EDRF), on the Ca(2+)-dependent K+ (KCa) channels in isolated cultured human pulmonary arterial smooth muscle cells (HPSMC). NO., SIN-1, and EDRF caused similar increases in KCa channel activity. Inhibiting cGMP generation with methylene blue or inhibiting the effect(s) of cGMP with the cGMP antagonist 8-bromoguanosine 3',5'-cyclic monophosphorothioate Rp isomer Rp-cGMPS prevented the NO.- and SIN-1-mediated activation of KCa channels, respectively. Treating the human pulmonary arterial endothelial cells with methylene blue blocked the EDRF-mediated activation of KCa channels in HPSMC. The cGMP analogue 8-bromo-cGMP increased KCa channel activity in intact cells and in excised inside-out HPSMC membrane patches. In the presence of cGMP and ATP, the alpha-isozyme of the cGMP-dependent protein kinase (I alpha-cGMP-PK) significantly increased KCa channel activity, and the channel activation was further increased on addition of the protein phosphatase inhibitors okadaic acid and calyculin A. Furthermore, the cGMP-mediated KCa channel activation was reduced by the cyclic nucleotide-dependent protein kinase inhibitor N-[2-methylamino)ethyl]-5-isoquinlinesulfonamide (H-8). Thus, in HPSMC, the mechanism of NO.- and native EDRF-induced KCa channel activation appears to be mediated via cGMP-I alpha-cGMP-PK phosphorylation of KCa channels.
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Pérez, Guillermo J. "Dual Effect of Tamoxifen on Arterial KCa Channels Does Not Depend on the Presence of the β1 Subunit." Journal of Biological Chemistry 280, no. 23 (April 11, 2005): 21739–47. http://dx.doi.org/10.1074/jbc.m413953200.
Full textAbstract:
Tamoxifen has been reported to directly activate large conductance calcium-activated potassium (KCa) channels through the KCa β1 subunit, suggesting a cardio-protective role of this compound. The present study using knock-out (KO) mice for the KCa channel β1 subunit was aimed at understanding the molecular mechanisms of the effects of tamoxifen on arterial smooth muscle KCa channels. Single channel studies were conducted in excised patches from cerebral artery myocytes from both wild-type and KO animals. The present data demonstrated that tamoxifen can inhibit arterial KCa channels due to a major decrease in channel open probability (Po), a mechanism different from the reduction in single channel amplitude reported previously and also observed in the present work. A tamoxifen-induced decrease in Po was present in arterial KCa channels from both wild-type and β1 KO animals. This inhibition was concentration-dependent and partially reversible with a half-maximal concentration constant IC50 of 2.6 μm. The effect of tamoxifen was actually dual Single channel kinetic analysis showed that tamoxifen shortens both mean closed time and mean open time; the latter is probably due to an intermediate duration voltage-independent blocking mechanism. Thus, tamoxifen block would predominate when KCa channel Po is >0.1–0.2, limiting the maximum Po, whereas a leftward shift in voltage or Ca2+ activation curves can be observed for Po values lower than those values. This dual effect of tamoxifen appears to be independent of the β1 subunit. The molecular specificity of tamoxifen, or eventually other xenoestrogen derivatives, for the KCa channel β1 subunit is uncertain.
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Бойко, В. А., С. В. Левченко, Д. Ю. Белаш, and А. В. Романов. "Aerosol treatments as a way to increase the storage stability of table grapes." Magarach Vinogradstvo i Vinodelie, no. 2(120) (June 16, 2022): 154–59. http://dx.doi.org/10.35547/im.2022.46.92.009.
Full textAbstract:
В рамках существующей технологии длительного хранения столового винограда актуальной задачей является регулирование биохимических процессов в ягоде при хранении. Перспективными способами её решения являются послеуборочные обработки винограда биологически активными препаратами. В данной работе изучено влияние аэрозольных обработок препаратами Brentax KCa и аскорбиновая кислота + кадифит (АК+К) на повышение лежкоспособности столовых сортов винограда. Исследования проводились в 2019-2020 гг., в условиях горно-долинного приморского виноградарского района Республики Крым, на столовых сортах винограда Молдова, Шоколадный и Ред Глоуб. Обработки позволили снизить активность фермента полифенолоксидаза: Brentax KCa на 7-25%; АК+К на 9-41%. Отмечено снижение естественной убыли массы у исследуемых сортов: Молдова - 24-35%; Шоколадный - 6-12%; Ред Глоуб - 24-25%. Обработка препаратом Brentax KCa способствовала снижению интенсивности дыхания на 21-43% в зависимости от сорта, препаратом АК+К - на 16-47%, соответственно. Опытные образцы характеризовались более высокой дегустационной оценкой: Шоколадный - 8,2 (Brentax KCa) - 8,4 (АК+К) балла; Ред Глоуб - 8,1 (Brentax KCa) - 8,5 (АК+К) балла; Молдова - 8,1 (Brentax KCa) - 8,3 (АК+К) балла. В среднем опытные образцы превосходили контроль на 4-7% за счет сохранности внешнего вида грозди и гребня, окраски, тургора ягод и гармоничности вкуса. Within the framework of existing technology of long-term storage of table grapes, an urgent task is to regulate biochemical processes in a berry during storage. Promising ways of solution are post-harvest treatments of grapes with biologically active preparations. In this paper, we have studied the effect of aerosol treatments with preparations Brentax KCa and Ascorbic Acid+Kadifit (AA+K) on increasing the storage stability of table grapevine cultivars. The studies were carried out in 2019-2020, in conditions of the mountain-valley coastal viticultural region of the Republic of Crimea, on table grapevine cultivars ‘Moldova’, ‘Shokoladnyi’ and ‘Red Globe’. Treatments made it possible to reduce the activity of polyphenoloxidase enzyme: Brentax KCa by 7-25%; AA+K by 9-41%. A decrease in the natural weight loss of the studied cultivars was observed: ‘Moldova’ - 24-35%; ‘Shokoladnyi’ - 6-12%; ‘Red Globe’ - 24-25%. Treatment with Brentax KCa preparation contributed to a decrease in respiration intensity by 21-43%, depending on the cultivar, and with AA+K - by 16-47%, respectively. Experimental samples were characterized by a higher tasting assessment: ‘Shokoladnyi’ - 8.2 (Brentax KCa) and 8.4 (AA+K) points; ‘Red Globe’ - 8.1 (Brentax KCa) and 8.5 (AA+K) points; ‘Moldova’ - 8.1 (Brentax KCa) and 8.3 (AA+K) points. On average, the experimental samples exceeded the control by 4-7% due to preserving bunch and stem appearance, color, turgor of berries, and balanced flavor.
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Merkus, Daphne, Oana Sorop, Birgit Houweling, Bas A. Hoogteijling, and Dirk J. Duncker. "KCa+ channels contribute to exercise-induced coronary vasodilation in swine." American Journal of Physiology-Heart and Circulatory Physiology 291, no. 5 (November 2006): H2090—H2097. http://dx.doi.org/10.1152/ajpheart.00315.2006.
Full textAbstract:
Coronary blood flow is controlled via several vasoactive mediators that exert their effect on coronary resistance vessel tone through activation of K+ channels in vascular smooth muscle. Because Ca2+-activated K+ (KCa+) channels are the predominant K+ channels in the coronary vasculature, we hypothesized that KCa+ channel activation contributes to exercise-induced coronary vasodilation. In view of previous observations that ATP-sensitive K+ (KATP+) channels contribute, in particular, to resting coronary resistance vessel tone, we additionally investigated the integrated control of coronary tone by KCa+ and KATP+ channels. For this purpose, the effect of KCa+ blockade with tetraethylammonium (TEA, 20 mg/kg iv) on coronary vasomotor tone was assessed in the absence and presence of KATP+ channel blockade with glibenclamide (3 mg/kg iv) in chronically instrumented swine at rest and during treadmill exercise. During exercise, myocardial O2 delivery increased commensurately with the increase in myocardial O2 consumption, so that myocardial O2 extraction and coronary venous Po2 ([Formula: see text]) were maintained constant. TEA (in a dose that had no effect on KATP+ channels) had a small effect on the myocardial O2 balance at rest and blunted the exercise-induced increase in myocardial O2 delivery, resulting in a progressive decrease of [Formula: see text] with increasing exercise intensity. Conversely, at rest glibenclamide caused a marked decrease in [Formula: see text] that waned at higher exercise levels. Combined KCa+ and KATP+ channel blockade resulted in coronary vasoconstriction at rest that was similar to that caused by glibenclamide alone and that was maintained during exercise, suggesting that KCa+ and KATP+ channels act in a linear additive fashion. In conclusion, KCa+ channel activation contributes to the metabolic coronary vasodilation that occurs during exercise. Furthermore, in swine KCa+ and KATP+ channels contribute to coronary resistance vessel control in a linear additive fashion.
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Van, Nhung Thi Hong, Woo Kyung Kim, and Joo Hyun Nam. "Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications." International Journal of Molecular Sciences 25, no. 5 (March 4, 2024): 2965. http://dx.doi.org/10.3390/ijms25052965.
Full textAbstract:
Calcium-activated potassium (KCa) channels are ubiquitously expressed throughout the body and are able to regulate membrane potential and intracellular calcium concentrations, thereby playing key roles in cellular physiology and signal transmission. Consequently, it is unsurprising that KCa channels have been implicated in various diseases, making them potential targets for pharmaceutical interventions. Over the past two decades, numerous studies have been conducted to develop KCa channel-targeting drugs, including those for disorders of the central and peripheral nervous, cardiovascular, and urinary systems and for cancer. In this review, we synthesize recent findings regarding the structure and activating mechanisms of KCa channels. We also discuss the role of KCa channel modulators in therapeutic medicine. Finally, we identify the major reasons behind the delay in bringing these modulators to the pharmaceutical market and propose new strategies to promote their application.
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Araujo, A., and J. W. Walker. "Kinetics of tension development in skinned cardiac myocytes measured by photorelease of Ca2+." American Journal of Physiology-Heart and Circulatory Physiology 267, no. 5 (November 1, 1994): H1643—H1653. http://dx.doi.org/10.1152/ajpheart.1994.267.5.h1643.
Full textAbstract:
The rate of activation of tension development by free Ca2+ was examined in skinned rat ventricular myocytes. Pulse photolysis of the photosensitive Ca2+ chelator, Nitr-7, was used to rapidly elevate Ca2+ in the vicinity of the myofilaments. Tension increased exponentially with a first-order rate constant (kCa) that depended on the level of Ca2+ activation. kCa increased approximately linearly from 0.9 +/- 0.2 s-1 at 20% maximal Ca(2+)-activated tension (Po) to 4.0 +/- 0.9 s-1 at 85% Po, representing a fourfold increase in kCa with activation. Reducing free Mg2+ from 1 to 0.1 mM accelerated kCa by about twofold at all levels of Ca2+. Tension development kinetics were significantly different in skinned rabbit psoas fibers: kCa increased nonlinearly from 1.2 +/- 0.2 s-1 at 15% Po to a maximum of 17.5 +/- 1.3 s-1 at 85% Po, representing a 15-fold increase in kCa with activation. Moreover, lowering free Mg2+ increased kCa only at submaximal Ca2+ in psoas fibers. Extraction of troponin C (TNC) from psoas fibers and recombination with bovine cardiac TNC did not significantly alter any of these characteristics of tension development kinetics. We conclude that significant differences exist between cardiac and fast-twitch skeletal muscles in terms of the effects of Ca2+ and Mg2+ on contraction kinetics and that these differences cannot be attributed solely to differences in TNC isoforms.
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Gebremedhin, Debebe, Ken Yamaura, and David R. Harder. "Role of 20-HETE in the hypoxia-induced activation of Ca2+-activated K+ channel currents in rat cerebral arterial muscle cells." American Journal of Physiology-Heart and Circulatory Physiology 294, no. 1 (January 2008): H107—H120. http://dx.doi.org/10.1152/ajpheart.01416.2006.
Full textAbstract:
The mechanism of sensing hypoxia and hypoxia-induced activation of cerebral arterial Ca2+-activated K+ (KCa) channel currents and vasodilation is not known. We investigated the roles of the cytochrome P-450 4A (CYP 4A) ω-hydroxylase metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), and generation of superoxide in the hypoxia-evoked activation of the KCa channel current in rat cerebral arterial muscle cells (CAMCs) and cerebral vasodilation. Patch-clamp analysis of K+ channel current identified a voltage- and Ca2+-dependent 238 ± 21-pS unitary K+ currents that are inhibitable by tetraethylammonium (TEA, 1 mM) or iberiotoxin (100 nM). Hypoxia (<2% O2) reversibly enhanced the open-state probability ( NPo) of the 238-pS unitary KCa current in cell-attached patches. This effect of hypoxia was not observed on unitary KCa currents recorded from either excised inside-out or outside-out membrane patches. Inhibition of CYP 4A ω-hydroxylase activity increased the NPo of KCa single-channel current. Hypoxia reduced the basal endogenous level of 20-HETE by 47 ± 3% as well as catalytic formation of 20-HETE in cerebral arterial muscle homogenates as determined by liquid chromatography-mass spectrometry analysis. The concentration of authentic 20-HETE was reduced when incubated with the superoxide donor KO2. Exogenous 20-HETE (100 nM) attenuated the hypoxia-induced activation of the KCa current in CAMCs. Hypoxia did not augment the increase in NPo of KCa channel current induced by suicide inhibition of endogenous CYP 4A ω-hydroxylase activity with 17-octadecynoic acid. In pressure (80 mmHg)-constricted cerebral arterial segments, hypoxia induced dilation that was partly attenuated by 20-HETE or by the KCa channel blocker TEA. Exposure to hypoxia caused the generation of intracellular superoxide as evidenced by intense staining of arterial muscle with the fluorescent probe hydroethidine, by quantitation using fluorescent HPLC analysis, and by attenuation of the hypoxia-induced activation of the KCa channel current by superoxide dismutation. These results suggest that the exposure of CAMCs to hypoxia results in the generation of superoxide and reduction in endogenous level of 20-HETE that may account for the hypoxia-induced activation of arterial KCa channel currents and cerebral vasodilation.
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Kanu, Alie, and Charles W. Leffler. "Carbon monoxide and Ca2+-activated K+ channels in cerebral arteriolar responses to glutamate and hypoxia in newborn pigs." American Journal of Physiology-Heart and Circulatory Physiology 293, no. 5 (November 2007): H3193—H3200. http://dx.doi.org/10.1152/ajpheart.00274.2007.
Full textAbstract:
Large-conductance calcium-activated potassium (KCa) channels regulate the physiological functions of many tissues, including cerebrovascular smooth muscle. l-Glutamic acid (glutamate) is the principal excitatory neurotransmitter in the central nervous system, and oxygen tension is a dominant local regulator of vascular tone. In vivo, glutamate and hypoxia dilate newborn pig cerebral arterioles, and both dilations are blocked by inhibition of carbon monoxide (CO) production. CO dilates cerebral arterioles by activating KCa channels. Therefore, the present study was designed to investigate the effects of glutamate and hypoxia on cerebral CO production and the role of KCa channels in the cerebral arteriolar dilations to glutamate and hypoxia. In the presence of iberiotoxin or paxilline that block dilation to the KCa channel opener, NS-1619, neither CO nor glutamate dilated pial arterioles. Conversely, neither paxilline nor iberiotoxin inhibited dilation to acute severe or moderate prolonged hypoxia. Both glutamate and hypoxia increased cerebrospinal fluid (CSF) CO concentration. Iberiotoxin that blocked dilation to glutamate did not attenuate the increase in CSF CO. The guanylyl cyclase inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), which blocked dilation to sodium nitroprusside, did not inhibit dilation to hypoxia. These data suggest that dilation of newborn pig pial arterioles to glutamate is mediated by activation of KCa channels, consistent with the intermediary signal being CO. Surprisingly, although 1) heme oxygenase (HO) inhibition attenuates dilation to hypoxia, 2) hypoxia increases CSF CO concentration, and 3) KCa channel antagonists block dilation to CO, neither KCa channel blockers nor ODQ altered dilation to hypoxia, suggesting the contribution of the HO/CO system to hypoxia-induced dilation is not by stimulating vascular smooth muscle KCa channels or guanylyl cyclase.
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Mallouk, Nora, and Bruno Allard. "Stretch-induced activation of Ca2+-activated K+ channels in mouse skeletal muscle fibers." American Journal of Physiology-Cell Physiology 278, no. 3 (March 1, 2000): C473—C479. http://dx.doi.org/10.1152/ajpcell.2000.278.3.c473.
Full textAbstract:
High-conductance Ca2+-activated K+(KCa) channels were studied in mouse skeletal muscle fibers using the patch-clamp technique. In inside-out patches, application of negative pressure to the patch induced a dose-dependent and reversible activation of KCa channels. Stretch-induced increase in channel activity was found to be of the same magnitude in the presence and in the absence of Ca2+ in the pipette. The dose-response relationships between KCa channel activity and intracellular Ca2+ and between KCa channel activity and membrane potential revealed that voltage and Ca2+ sensitivity were not altered by membrane stretch. In cell-attached patches, in the presence of high external Ca2+ concentration, stretch-induced activation was also observed. We conclude that membrane stretch is a potential mode of regulation of skeletal muscle KCa channel activity and could be involved in the regulation of muscle excitability during contraction-relaxation cycles.
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Perez, G., and L. Toro. "Differential modulation of large-conductance KCa channels by PKA in pregnant and nonpregnant myometrium." American Journal of Physiology-Cell Physiology 266, no. 5 (May 1, 1994): C1459—C1463. http://dx.doi.org/10.1152/ajpcell.1994.266.5.c1459.
Full textAbstract:
Uterine excitability depends on ion channel activity, the expression of which is regulated by sexual hormones. We show now that the action of protein kinase A (PKA) on large-conductance calcium-activated K+ (KCa) channel activity also depends on the hormonal status. PKA-dependent phosphorylation of reconstituted KCa channels from midpregnant rats usually stimulated channel activity; in contrast, KCa channels from nonpregnant rat and human myometrium were primarily inhibited by this mechanism. Both effects were reversible by phosphatase treatment. These results suggest that one important factor modulating uterine contractility during pregnancy or the regular cycle may be the differential response of KCa channels toward PKA-induced phosphorylation.
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Lu, Gang, Bruno Mazet, Michael G. Sarr, and Joseph H. Szurszewski. "Effect of nitric oxide on calcium-activated potassium channels in colonic smooth muscle of rabbits." American Journal of Physiology-Gastrointestinal and Liver Physiology 274, no. 5 (May 1, 1998): G848—G856. http://dx.doi.org/10.1152/ajpgi.1998.274.5.g848.
Full textAbstract:
Nitric oxide (NO) hyperpolarizes intestinal smooth muscle cells. This study was designed to determine the mechanism whereby NO activates KCa channels of circular smooth muscle of the rabbit colon. Transmural biopsies of the rabbit colon were stained for NADPH-diaphorase. Freshly dispersed circular smooth muscle cells were studied in the whole cell configuration, as well as in on-cell and excised inside-out patch recording configurations, while KCa current and the activity of KCa channels, respectively, were monitored. NADPH-diaphorase-positive nerve fibers were found in both muscle layers. NO (1%) increased whole cell net outward current by 79% and hyperpolarized resting membrane voltage from −59 to −73 mV ( n = 8 cells, P < 0.01). In the on-cell patch recording configuration, NO (0.5% or 1%) in the bath increased NP o of KCa channels; charybdotoxin (125 nM) in the pipette solution blocked this effect. In the excised inside-out patch recording configuration, NO (1%) had no effect on NP o of KCa channels. In the on-cell patch recording configuration, methylene blue (1 μM) or cystamine (5 mM) in the bath solution decreased the effect of NO (1%) on NP o of KCa channels. NP o was increased by 8-bromo-cGMP (8-BrcGMP; 1 mM), a cGMP analog, and zaprinast (100 μM), an inhibitor of cGMP phosphodiesterase. These data suggest that NO increased whole cell outward K+current by activating KCa channels through a cGMP pathway.
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Szado, Tania, Megan McLarnon, Xiaodong Wang, and Casey van Breemen. "Role of sarcoplasmic reticulum in regulation of tonic contraction of rabbit basilar artery." American Journal of Physiology-Heart and Circulatory Physiology 281, no. 4 (October 1, 2001): H1481—H1489. http://dx.doi.org/10.1152/ajpheart.2001.281.4.h1481.
Full textAbstract:
Superficial sarcoplasmic reticulum (SR) regulates smooth muscle force development directly by Ca2+ release and removal to and from the cytoplasm (Somlyo and Somlyo. J Cardiovasc Pharmacol 8, Suppl8: S42–S47, 1986) by buffering Ca2+ influx and contributing to Ca2+ extrusion (Mueller and van Breemen. Nature 281: 682–683, 1979) and indirectly by releasing Ca2+ near Ca2+-activated K+channels (KCa) to hyperpolarize the plasma membrane (Bolton and Imaizumi. Cell Calcium 20: 141–152, 1996 and Nelson et al. Science 270: 633–637, 1995). In the rabbit basilar artery, relative contributions of direct effects and those mediated through activation of KCa were evaluated by measuring force and intracellular Ca2+ concentration ([Ca2+]i) in response to the SR-depleting agents thapsigargin and ryanodine and the large conductance KCa (BKCa) blockers iberiotoxin (IbTX) and tetraethylammonium ion (TEA). A large contraction was observed in response to KCa blockade with either 3 mM TEA or 100 nM IbTX and also after addition of 10 μM ryanodine or 2 μM thapsigargin. When KCa was blocked first with TEA or IbTX, subsequent addition of thapsigargin or ryanodine also increased force. Measurements of fura 2 fluorescence showed parallel increases in [Ca2+]i in response to sequential blockade of sarco(endo)plasmic reticulum Ca2+-ATPase and KCa regardless of the order of application. It appears that a significant fraction of KCa remains activated in the absence of SR function and that SR contributes to relaxation after blockade of KCa. We found that depletion of SR before stimulating Ca2+ influx through voltage-gated Ca2+ channels markedly reduced force development rate and that thapsigargin abolished this effect. We conclude that the SR of rabbit cerebral arteries modulates constriction by direct and indirect mechanisms.
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Xi, Qi, Dilyara Tcheranova, Helena Parfenova, Burton Horowitz, Charles W. Leffler, and Jonathan H. Jaggar. "Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing apparent Ca2+ sensitivity of α-subunits." American Journal of Physiology-Heart and Circulatory Physiology 286, no. 2 (February 2004): H610—H618. http://dx.doi.org/10.1152/ajpheart.00782.2003.
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Carbon monoxide (CO) is a gaseous vasodilator produced by many cell types, including endothelial and smooth muscle cells. The goal of the present study was to investigate signaling mechanisms responsible for CO activation of large-conductance Ca2+-activated K+ (KCa) channels in newborn porcine cerebral arteriole smooth muscle cells. In intact cells at 0 mV, CO (3 μM) or CO released from dimanganese decacarbonyl (10 μM), a novel light-activated CO donor, increased KCa channel activity 4.9- or 3.5-fold, respectively. KCa channel activation by CO was not blocked by 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (25 μM), a soluble guanylyl cyclase inhibitor. In inside-out patches at 0 mV, CO shifted the Ca2+ concentration-response curve for KCa channels leftward and decreased the apparent dissociation constant for Ca2+ from 31 to 24 μM. Western blotting data suggested that the low Ca2+ sensitivity of newborn KCa channels may be due to a reduced β-subunit-to-α-subunit ratio. CO activation of KCa channels was Ca2+ dependent. CO increased open probability 3.7-fold with 10 μM free Ca2+ at the cytosolic membrane surface but only 1.1-fold with 300 nM Ca2+. CO left shifted the current-voltage relationship of cslo-α currents expressed in HEK-293 cells, increasing currents 2.2-fold at +50 mV. In summary, data suggest that in newborn arteriole smooth muscle cells, CO activates low-affinity KCa channels via a direct effect on the α-subunit that increases apparent Ca2+ sensitivity. The optimal tuning by CO of the micromolar Ca2+ sensitivity of KCa channels will lead to preferential activation by signaling modalities, such as Ca2+ sparks, which elevate the subsarcolemmal Ca2+ concentration within this range.
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Sahitya, U. Lakshmi, M. S. R. Krishna, R. Sri Deepthi, G. Shiva Prasad, and D. Peda Kasim. "Seed Antioxidants Interplay with Drought Stress Tolerance Indices in Chilli (Capsicum annuum L) Seedlings." BioMed Research International 2018 (2018): 1–14. http://dx.doi.org/10.1155/2018/1605096.
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Altering climatic conditions and water stress drastically affects the chilli crop yield. In this scenario we adapted a strategic approach for screening of elite chilli genotypes, by exploring role of seed antioxidants in stress tolerance during vegetative phase. A total of 20 chilli genotypes’ seed antioxidant potential and its effect on water stress tolerance were studied at three water regimes, namely, control (100% Field Capacity), moderate (80% Field Capacity), and severe (60% Field Capacity) stress conditions. Drought tolerance traits relative water content, chlorophyll content, and activities of superoxide dismutase and catalase enzymes were measured. A strong correlation was observed between seed antioxidants and water stress tolerant traits in seedlings. Genotypes KCa-5, KCa-6, and KCa-10 showed low quantity of H2O2 and Malondialdehyde in seeds and maintained high membrane integrity and chlorophyll content in seedlings. High content of proline in KCa-5, KCa-7, and KCa-10 seeds retained high relative water content at seedling stage under severe water stress. Present work reveals genotypic differences of hot pepper to different water regimes. Based on Principal Component Analysis (PCA) of seed antioxidant variables and drought tolerance indices twenty genotypes segregated into three clusters, namely, drought tolerant and susceptible and moderately tolerant.
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Scornik, F. S., J. Codina, L. Birnbaumer, and L. Toro. "Modulation of coronary smooth muscle KCa channels by Gs alpha independent of phosphorylation by protein kinase A." American Journal of Physiology-Heart and Circulatory Physiology 265, no. 4 (October 1, 1993): H1460—H1465. http://dx.doi.org/10.1152/ajpheart.1993.265.4.h1460.
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The occupancy of beta-receptors in the smooth muscle membrane of the coronary arteries produces vasodilation and a concomitant hyperpolarization. Large conductance calcium-activated K (KCa) channels are likely to be involved in such hyperpolarization, since they are densely distributed in coronary myocytes, and they are targets of beta-adrenergic stimulation in other smooth muscles. We sought to explore if coronary smooth muscle KCa channels are modulated by beta-agonists and we studied the mechanisms of their activation. We found that KCa channels reconstituted into lipid bilayers were activated in the presence of GTP by the beta-adrenergic receptor agonist isoproterenol. KCa channels were also stimulated on non-specific activation of an endogenous G protein(s) with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), on addition of a purified activated stimulatory G protein (Gs alpha), and when the catalytic subunit of protein kinase A (PKA) was added. Inhibition of PKA activity prevented KCa channel stimulation by PKA, but not by endogenous G protein or by exogenous Gs alpha. These results indicate that beta-adrenoceptor activation of coronary smooth muscle KCa channels results from a dual control: 1) a membrane delimited, possibly direct action of Gs, independent of PKA-mediated phosphorylation; and 2) by PKA-dependent phosphorylation.
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Khaddaj Mallat, Rayan, Cini Mathew John, Ramesh C. Mishra, Dylan J. Kendrick, and Andrew P. Braun. "Pharmacological Targeting of KCa Channels to Improve Endothelial Function in the Spontaneously Hypertensive Rat." International Journal of Molecular Sciences 20, no. 14 (July 16, 2019): 3481. http://dx.doi.org/10.3390/ijms20143481.
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Systemic hypertension is a major risk factor for the development of cardiovascular disease and is often associated with endothelial dysfunction. KCa2.3 and KCa3.1 channels are expressed in the vascular endothelium and contribute to stimulus-evoked vasodilation. We hypothesized that acute treatment with SKA-31, a selective activator of KCa2.x and KCa3.1 channels, would improve endothelium-dependent vasodilation and transiently lower mean arterial pressure (MAP) in male, spontaneously hypertensive rats (SHRs). Isolated vascular preparations exhibited impaired vasodilation in response to bradykinin (i.e., endothelial dysfunction) compared with Wistar controls, which was associated with decreased bradykinin receptor expression in mesenteric arteries. In contrast, similar levels of endothelial KCa channel expression were observed, and SKA-31 evoked vasodilation was comparable in vascular preparations from both strains. Addition of a low concentration of SKA-31 (i.e., 0.2–0.3 μM) failed to augment bradykinin-induced vasodilation in arteries from SHRs. However, responses to acetylcholine were enhanced. Surprisingly, acute bolus administration of SKA-31 in vivo (30 mg/kg, i.p. injection) modestly elevated MAP compared with vehicle injection. In summary, pharmacological targeting of endothelial KCa channels in SHRs did not readily reverse endothelial dysfunction in situ, or lower MAP in vivo. SHRs thus appear to be less responsive to endothelial KCa channel activators, which may be related to their vascular pathology.
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Lhuillier, Loic, and Stuart E. Dryer. "TGFβ1 Regulates the Gating Properties of Intermediate-Conductance KCa Channels in Developing Parasympathetic Neurons." Journal of Neurophysiology 82, no. 3 (September 1, 1999): 1627–31. http://dx.doi.org/10.1152/jn.1999.82.3.1627.
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The developmental expression of Ca2+-activated K+ channels (KCa) in chick ciliary ganglion (CG) neurons is regulated by a target-derived avian isoform of TGFβ1, which evokes a robust increase in the number of functional large-conductance (BK) KCa channels but which produces no change in their kinetics. However, CG neurons express multiple KCa channel subtypes. Here we show that TGFβ1 regulates the gating properties of intermediate-conductance (IK) KCachannels in developing CG neurons. IK channels in inside-out patches excised from control E9 CG neurons became active on exposure to 1–5 μM free Ca2+ but then remained active on return to Ca2+-free salines. In contrast, IK channels in TGFβ1-treated cells became active on exposure to 1–5 μM Ca2+, but became quiescent immediately on return to Ca2+-free salines. In contrast to its effects on BK channels, TGFβ1 had no effect on the mean number of IK channels detected in excised patches. IK channels were not activated in cell-attached patches on E9 neurons depolarized by bath application of 145 mM KCl in the presence of 5 mM external Ca2+. However, BK channels were activated immediately by this procedure and were detected at a higher density in TGFβ1-treated cells. In addition, analyses of macroscopic KCa fluctuations, and the voltage-dependence of KCa tail currents, suggest that IK channels do not contribute to voltage-evoked whole cell KCa. IK channels therefore may have some other function. These results indicate that the effects of TGFβ1 on CG neurons entail distinct actions on multiple KCa channel subtypes.
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Devor, Daniel C., and Raymond A. Frizzell. "Modulation of K+ channels by arachidonic acid in T84 cells. I. Inhibition of the Ca2+-dependent K+ channel." American Journal of Physiology-Cell Physiology 274, no. 1 (January 1, 1998): C138—C148. http://dx.doi.org/10.1152/ajpcell.1998.274.1.c138.
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The Cl− secretory response of colonic cells to Ca2+-mediated agonists is transient despite a sustained elevation of intracellular Ca2+. We evaluated the effects of second messengers proposed to limit Ca2+-mediated Cl− secretion on the basolateral membrane, Ca2+-dependent K+ channel (KCa) in colonic secretory cells, T84. Neither protein kinase C (PKC) nor inositol tetrakisphosphate (1,3,4,5 or 3,4,5,6 form) affected KCa in excised inside-out patches. In contrast, arachidonic acid (AA; 3 μM) potently inhibited KCa, reducing NP o, the product of number of channels and channel open probability, by 95%. The apparent inhibition constant for this AA effect was 425 nM. AA inhibited KCa in the presence of both indomethacin and nordihydroguaiaretic acid, blockers of the cyclooxygenase and lipoxygenase pathways. In the presence of albumin, the effect of AA on KCa was reversed. A similar effect of AA was observed on KCa during outside-out recording. We determined also the effect of the cis-unsaturated fatty acid linoleate, the trans-unsaturated fatty acid elaidate, and the saturated fatty acid myristate. At 3 μM, all of these fatty acids inhibited KCa, reducing NP o by 72–86%. Finally, the effect of the cytosolic phospholipase A2 inhibitor arachidonyltrifluoromethyl ketone (AACOCF3) on the carbachol-induced short-circuit current ( I sc) response was determined. In the presence of AACOCF3, the peak carbachol-induced I sc response was increased ∼2.5-fold. Our results suggest that AA generation induced by Ca2+-mediated agonists may contribute to the dissociation observed between the rise in intracellular Ca2+ evoked by these agonists and the associated Cl− secretory response.
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Cobbinah, Patrick Brandful. "Local attitudes towards natural resources management in rural Ghana." Management of Environmental Quality: An International Journal 26, no. 3 (April 13, 2015): 423–36. http://dx.doi.org/10.1108/meq-04-2014-0061.
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Purpose – Local support is fundamental in natural resources management (NRM). However, recent studies indicate that NRM in protected areas in developing countries is often faced with local resistance due to its impacts on livelihoods. The purpose of this paper is to examine local attitudes – positive and negative responses – towards NRM in protected areas and implications of NRM benefits on local support for conservation of protected areas. Design/methodology/approach – A quantitative research method was used for this study. Structured questionnaire survey was administered to 310 respondents across four case study communities – Abrafo, Mesomagor, Adadientem and Nuamakrom – around the Kakum Conservation Area (KCA), Ghana. χ2 test and logistic regression were used to analyse the data with the aid of Statistical Package for Social Sciences (SPSS) software. Findings – Findings showed positive attitudes towards NRM in protected areas (85.9 per cent) and high support for conservation of KCA (86.5 per cent). Respondents recognised the importance of the KCA in managing natural resources especially forest and water resources. Positive attitudes towards conservation of KCA were largely influenced by receipt of socio-economic benefits from the KCA, in terms of employment, income and involvement in KCA management. However, those excluded from socio-economic benefits from the KCA also expressed positive attitudes towards conservation, suggesting that support for NRM transcends socio-economic benefits. On the other hand, local people recognised the challenges associated with NRM in protected areas such as increased farm raids by wildlife, loss of access to timber and non-timber forest products. Originality/value – This paper has revealed that although socio-economic benefits from NRM in protected areas influence local people’s support for conservation, local knowledge of the environmental benefits is equally important. The depth of local knowledge of NRM in the KCA is dependent on educational status and level of involvement of respondents in the KCA in terms of employment, and the effectiveness of educational campaigns by the park officials. Therefore, in the absence of clear development programmes from government and park officials to educate and involve local people in NRM, it appears the conservation objective upon which NRM in protected areas are designed may not be realised.
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Fedo, Ermelinda, Laurentius D. Gadi Djou, and Sesilianus Kapa. "PENGARUH PEMBERIAN KREDIT GADAI KCA TERHADAP PENDAPATAN SEWA MODAL DI PT PEGADAIAN CABANG WOLOWONA KABUPATEN ENDE." Jurnal Riset Ilmu Akuntansi 1, no. 2 (June 7, 2022): 32–39. http://dx.doi.org/10.37478/jria.v1i2.1154.
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The problems that occur are what is the level of KCA pawning credit, how is the level of capital lease income and how much influence does KCA pawning credit give to capital lease income at PT Pegadaian, Wolowona branch. This study aims to determine the level of KCA pawning credit at PT Pegadaian, Wolowona branch, the level of capital rental income at PT Pegadaian, Wolowona branch, and the effect of KCA pawning credit on rental income at PT Pegadaian, Wolowona branch. The method in this study uses simple linear regression analysis, t test, and the coefficient of reduction to determine the effect of KCA pawning credit on capital rental income at PT Pegadaian, Wolowona branch, Ende district. The data sources are primary data and secondary data. Data collection techniques in this study were observation, interviews, and documentation. Based on the test results using simple linear analysis, t test, and determinant coefficient, it shows that the provision of mortgage loans has a significant effect on capital rental income at PT Pegadaian, Wolowona branch, Ende district.
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Vasileva, Valeria Y., Zuleikha M. Khairullina, Anastasia V. Sudarikova, and Vladislav I. Chubinskiy-Nadezhdin. "Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells." Membranes 13, no. 6 (June 4, 2023): 583. http://dx.doi.org/10.3390/membranes13060583.
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Calcium-activated potassium channels (KCa) are important participants in calcium signaling pathways due to their ability to be activated by an increase in intracellular free calcium concentration. KCa channels are involved in the regulation of cellular processes in both normal and pathophysiological conditions, including oncotransformation. Previously, using patch-clamp, we registered the KCa currents in the plasma membrane of human chronic myeloid leukemia K562 cells, whose activity was controlled by local Ca2+ entry via mechanosensitive calcium-permeable channels. Here, we performed the molecular and functional identification of KCa channels and have uncovered their role in the proliferation, migration and invasion of K562 cells. Using a combined approach, we identified the functional activity of SK2, SK3 and IK channels in the plasma membrane of the cells. Selective SK and IK channel inhibitors, apamin and TRAM-34, respectively, reduced the proliferative, migratory and invasive capabilities of human myeloid leukemia cells. At the same time, the viability of K562 cells was not affected by KCa channel inhibitors. Ca2+ imaging showed that both SK and IK channel inhibitors affect Ca2+ entry and this could underlie the observed suppression of pathophysiological reactions of K562 cells. Our data imply that SK/IK channel inhibitors could be used to slow down the proliferation and spreading of chronic myeloid leukemia K562 cells that express functionally active KCa channels in the plasma membrane.
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Chae, Kwon-Seok, Kwang-Seok Oh, and Stuart E. Dryer. "Growth Factors Mobilize Multiple Pools of KCa Channels in Developing Parasympathetic Neurons: Role of ADP-Ribosylation Factors and Related Proteins." Journal of Neurophysiology 94, no. 2 (August 2005): 1597–605. http://dx.doi.org/10.1152/jn.00296.2005.
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In developing ciliary ganglion (CG) neurons, movement of functional large-conductance (BK type) Ca2+-activated K+ ( KCa) channels to the cell surface is stimulated by the endogenous growth factors TGFβ1 and β-neuregulin-1 (NRG1). Here we show that a brief NRG1 treatment (0.5–1.5 h) mobilizes KCa channels in a post-Golgi compartment, but longer treatments (>3.5 h) mobilize KCa channels located in the endoplasmic reticulum or Golgi apparatus. Specifically, the effects of 3.5 h NRG1 treatment were completely blocked by treatments that disrupt Golgi apparatus function. These include inhibition of microtubules, or inhibition of the ADP-ribosylation factor-1 (ARF1) system by brefeldin A, by over-expression of dominant-negative ARF1, or over-expression of an ARF1 GTPase-activating protein that blocks ARF1 cycling between GTP- and GDP-bound states. These treatments had no effect on stimulation of KCa evoked by 1.5 h treatment with NRG1, indicating that short-term responses to NRG1 do not require an intact Golgi apparatus. By contrast, both the acute and sustained effects of NRG1 were inhibited by treatments that block trafficking processes that occur close to the plasma membrane. Thus mobilization of KCa was blocked by treatments than inhibit ADP-ribosylation factor-6 (ARF6) signaling, including overexpression of dominant-negative ARF6, dominant-negative ARNO, or dominant-negative phospholipase D1. TGFβ1, the effects of which on KCa are much slower in onset, is unable to selectively mobilize channels in the post-Golgi pool, and its effects on KCa are completely blocked by inhibition of microtubules, Golgi function and also by plasma membrane ARF6 and phospholipase D1 signaling.
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Marino, M., J. L. Bény, A. C. Peyter, R. Bychkov, G. Diaceri, and J. F. Tolsa. "Perinatal hypoxia triggers alterations in K+ channels of adult pulmonary artery smooth muscle cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 293, no. 5 (November 2007): L1171—L1182. http://dx.doi.org/10.1152/ajplung.00126.2007.
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Adverse events during the perinatal period, like hypoxia, have been associated with adult diseases. In pulmonary vessels, K+ channels play an important role in the regulation of vascular tone. In the fetus, Ca2+-activated K+ channels (KCa) are predominant, whereas from birth voltage-gated K+ channels (KV) prevail in the adult. We postulated that perinatal hypoxia could alter this maturational shift and influence regulation of pulmonary vascular tone in relation to K+ channels in adulthood. We evaluated the effects of perinatal hypoxia on KV and KCa channels in the adult main pulmonary artery (PA) using a murine model. Electrophysiological measurements showed a greater outward current in PA smooth muscle cells of mice born in hypoxia than in controls. In controls, only KV channels contributed to this current, whereas in mice born in hypoxia both KV and KCa channels were implicated. KV channel activity was even higher in mice born in hypoxia than in controls. Therefore, perinatal hypoxia results in increased KCa and KV channel activity in adult PA. Moreover, PA of adults born in hypoxia displayed higher large-conductance KCa α-subunit and KV1.5 α-subunit protein expression than controls. Interestingly, relaxation induced by nitric oxide (NO) donors [ S-nitroso- N-acetyl-D,l-penicillamine, 2-( N, N-diethylamino)-diazenolate-2-oxide] in isolated PA of control mice was not mediated by KCa channels and only slightly by KV channels, whereas following perinatal hypoxia both KCa and KV channels contributed to this relaxation. Thus perinatal hypoxia results in altered expression and activity of different K+ channels in the adult main PA, which could contribute to modifications of pulmonary vasoreactivity.
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Toro, L., J. Ramos-Franco, and E. Stefani. "GTP-dependent regulation of myometrial KCa channels incorporated into lipid bilayers." Journal of General Physiology 96, no. 2 (August 1, 1990): 373–94. http://dx.doi.org/10.1085/jgp.96.2.373.
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The regulation of calcium-activated K (KCa) channels by a G protein-mediated mechanism was studied. KCa channels were reconstituted in planar lipid bilayers by fusion of membrane vesicles from rat or pig myometrium. The regulatory process was studied by exploring the actions of GTP and GTP gamma S on single channel activity. KCa channels had a conductance of 260 +/- 6 pS (n = 25, +/- SE, 250/50 mM KCl gradient) and were voltage dependent. The open probability (Po) vs. voltage relationships were well fit by a Boltzmann distribution. The slope factor (11 mV) was insensitive to internal Ca2+. The half activation potential (V1/2) was shifted -70 mV by raising internal Ca2+ from pCa 6.2 to pCa 4. Addition of GTP or GTP gamma S activated channel activity only in the presence of Mg2+, a characteristic typical of G protein-mediated mechanisms. The Po increased from 0.18 +/- 0.08 to 0.49 +/- 0.07 (n = 7, 0 mV, pCa 6 to 6.8). The channel was also activated (Po increased from 0.03 to 0.37) in the presence of AMP-PNP, a nonphosphorylating ATP analogue, suggesting a direct G protein gating of KCa channels. Upon nucleotide activation, mean open time increased by a factor of 2.7 +/- 0.7 and mean closed time decreased by 0.2 +/- 0.07 of their initial values (n = 6). Norepinephrine (NE) or isoproterenol potentiated the GTP-mediated activation of KCa channels (Po increased from 0.17 +/- 0.06 to 0.35 +/- 0.07, n = 10). These results suggest that myometrium possesses beta-adrenergic receptors coupled to a GTP-dependent protein that can directly gate KCa channels. Furthermore, KCa channels, beta-adrenergic receptors, and G proteins can be reconstituted in lipid bilayers as a stable, functionally coupled, molecular complex.
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Guéguinou, Maxime, Aurélie Chantôme, Gaëlle Fromont, Philippe Bougnoux, Christophe Vandier, and Marie Potier-Cartereau. "KCa and Ca2+ channels: The complex thought." Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1843, no. 10 (October 2014): 2322–33. http://dx.doi.org/10.1016/j.bbamcr.2014.02.019.
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Feetham, Claire H., Rebecca Lewis, and Richard Barrett-Jolley. "TRPV4 and KCa: Modelling the Perfect Couple?" Biophysical Journal 104, no. 2 (January 2013): 163a. http://dx.doi.org/10.1016/j.bpj.2012.11.918.
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Su, Christina, Erin Linnenbringer, Danuta Dynda, Kristin Delfino, Sarah Lyons, Sharon Kim, Shaheen Alanee, and Kevin McVary. "Urban-rural kidney cancer disparities: The role of health literacy, cancer literacy, smoking status, and urinary bother." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e16513-e16513. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16513.
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e16513 Background: Kidney cancer (KCa) does not currently have efficacious screening methods, therefore targeting modifiable risk factors is a strong approach to primary prevention. Prior research from our group identified a significant difference in KCa incidence and mortality between the urban and rural populations in Illinois, but the reason(s) for this geographic variation were unclear. The objective of this pilot study was to investigate KCa-relevant knowledge and health behaviors in order to explain our observed urban-rural differences in KCa incidence and mortality, and to inform approaches to KCa prevention. Methods: A convenience sample was surveyed from five study sites between June 2016 and February 2018. These included 207 urban and 53 rural patients presenting at urology and primary care clinics. Four outcome measures related to KCa were assessed using validated measures: 1) health literacy, 2) cancer health literacy, 3) smoking status and knowledge of its association with KCa, and 4) degree of bother caused by urologic symptoms. Multivariate logistic regression models were used to examine these outcome measures between the two populations. Smoking history, personal and family history of cancer, and socio-demographic characteristics were controlled for in the analysis. Results: The overall model for predicting health literacy was significant (Wald Pvalue = 0.0269). When accounting for all covariates, rural versus urban residence was not a significant predictor of adequate health literacy (p = 0.4871). However, participants with higher levels of education (p = 0.0005), higher household income (p = 0.0395), and participants who were female (p = 0.0104) were all more likely to have adequate vs. low health literacy. We did not identify a statistically significant difference in cancer health literacy, knowledge of smoking as a KCa risk factor, or measurement of urinary bother between urban and rural residents in this population. Conclusions: The analyses revealed significant differences in health literacy by education, income, and gender, but not by geographic location. While there were no statistically significant geographical differences found in three of our four domains, this may have been attributed to the low proportion of rural-residing clinic patients recruited in this study. With potential limitations of using RUCA as a measure of rurality, future work is needed to better reach this population and validate results to understand the disparity of improving KCa outcomes in rural areas.
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Su, Christina, Erin Linnenbringer, Danuta Dynda, Kristin Delfino, Sarah Lyons, Sharon Kim, Shaheen Alanee, and Kevin McVary. "Urban-rural kidney cancer disparities: The role of health literacy, cancer literacy, smoking status, and urinary bother." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e16513-e16513. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16513.
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e16513 Background: Kidney cancer (KCa) does not currently have efficacious screening methods, therefore targeting modifiable risk factors is a strong approach to primary prevention. Prior research from our group identified a significant difference in KCa incidence and mortality between the urban and rural populations in Illinois, but the reason(s) for this geographic variation were unclear. The objective of this pilot study was to investigate KCa-relevant knowledge and health behaviors in order to explain our observed urban-rural differences in KCa incidence and mortality, and to inform approaches to KCa prevention. Methods: A convenience sample was surveyed from five study sites between June 2016 and February 2018. These included 207 urban and 53 rural patients presenting at urology and primary care clinics. Four outcome measures related to KCa were assessed using validated measures: 1) health literacy, 2) cancer health literacy, 3) smoking status and knowledge of its association with KCa, and 4) degree of bother caused by urologic symptoms. Multivariate logistic regression models were used to examine these outcome measures between the two populations. Smoking history, personal and family history of cancer, and socio-demographic characteristics were controlled for in the analysis. Results: The overall model for predicting health literacy was significant (Wald Pvalue = 0.0269). When accounting for all covariates, rural versus urban residence was not a significant predictor of adequate health literacy (p = 0.4871). However, participants with higher levels of education (p = 0.0005), higher household income (p = 0.0395), and participants who were female (p = 0.0104) were all more likely to have adequate vs. low health literacy. We did not identify a statistically significant difference in cancer health literacy, knowledge of smoking as a KCa risk factor, or measurement of urinary bother between urban and rural residents in this population. Conclusions: The analyses revealed significant differences in health literacy by education, income, and gender, but not by geographic location. While there were no statistically significant geographical differences found in three of our four domains, this may have been attributed to the low proportion of rural-residing clinic patients recruited in this study. With potential limitations of using RUCA as a measure of rurality, future work is needed to better reach this population and validate results to understand the disparity of improving KCa outcomes in rural areas.
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Jeremy, Richmond W., and Hugh McCarron. "Effect of hypercholesterolemia on Ca2+-dependent K+ channel-mediated vasodilatation in vivo." American Journal of Physiology-Heart and Circulatory Physiology 279, no. 4 (October 1, 2000): H1600—H1608. http://dx.doi.org/10.1152/ajpheart.2000.279.4.h1600.
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Nitric oxide (NO)-mediated and NO-independent mechanisms of endothelium-dependent vasodilatation involve Ca2+-dependent K+ (KCa) channels. We examined the role in vivo of KCa channels in NO-independent vasodilatation in hypercholesterolemia. Hindlimb vascular conductance was measured at rest and after aortic injection of ACh, bradykinin (BK), and sodium nitroprusside in anesthetized control and cholesterol-fed rabbits. Conductances were measured before and after treatment with the NO synthase antagonist N ω-nitro-l-arginine methyl ester (l-NAME, 10 mg/kg) or KCa blockers tetraethylammonium (30 mg/kg), charybdotoxin (10 μg/kg), and apamin (50 μg/kg). The contribution of NO to basal conductance was greater in control than in cholesterol-fed rabbits [2.2 ± 0.4 vs. 1.1 ± 0.3 (SE) ml · min−1 · kg−1 · 100 mmHg−1, P < 0.05], but the NO-independent KCa channel-mediated component was greater in the cholesterol-fed than in the control group (1.1 + 0.4 vs. 0.3 ± 0.1 ml · min−1 · kg−1 · 100 mmHg−1, P < 0.05). Maximum conductance response to ACh and BK was less in cholesterol-fed than in control rabbits, and the difference persisted after l-NAME (ACh: 7.7 ± 0.7 vs. 10.1 ± 0.5 ml · min−1 · kg−1 · 100 mmHg−1, P < 0.005). Blockade of KCa channels with tetraethylammonium or charybdotoxin + apamin almost completely abolished l-NAME-resistant vasodilatation after ACh or BK. The magnitude of KCa-mediated vasodilatation after ACh or BK was impaired in hypercholesterolemic rabbits. Vasodilator responses to nitroprusside did not differ between groups. In vivo , hypercholesterolemia is associated with an altered balance between NO-mediated and NO-independent KCa channel contributions to resting vasomotor tone and impairment of both mechanisms of endothelium-dependent vasodilatation.
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Benton, Mark D., Amanda H. Lewis, Jason S. Bant, and Indira M. Raman. "Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata." Journal of Neurophysiology 109, no. 10 (May 15, 2013): 2528–41. http://dx.doi.org/10.1152/jn.00127.2012.
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Purkinje cells have specialized intrinsic ionic conductances that generate high-frequency action potentials. Disruptions of their Ca or Ca-activated K (KCa) currents correlate with altered firing patterns in vitro and impaired motor behavior in vivo. To examine the properties of somatic KCa currents, we recorded voltage-clamped KCa currents in Purkinje cell bodies isolated from postnatal day 17–21 mouse cerebellum. Currents were evoked by endogenous Ca influx with approximately physiological Ca buffering. Purkinje somata expressed voltage-activated, Cd-sensitive KCa currents with iberiotoxin (IBTX)-sensitive (>100 nS) and IBTX-insensitive (>75 nS) components. IBTX-sensitive currents activated and partially inactivated within milliseconds. Rapid, incomplete macroscopic inactivation was also evident during 50- or 100-Hz trains of 1-ms depolarizations. In contrast, IBTX-insensitive currents activated more slowly and did not inactivate. These currents were insensitive to the small- and intermediate-conductance KCa channel blockers apamin, scyllatoxin, UCL1684, bicuculline methiodide, and TRAM-34, but were largely blocked by 1 mM tetraethylammonium. The underlying channels had single-channel conductances of ∼150 pS, suggesting that the currents are carried by IBTX-resistant (β4-containing) large-conductance KCa (BK) channels. IBTX-insensitive currents were nevertheless increased by small-conductance KCa channel agonists EBIO, chlorzoxazone, and CyPPA. During trains of brief depolarizations, IBTX-insensitive currents flowed during interstep intervals, and the accumulation of interstep outward current was enhanced by EBIO. In current clamp, EBIO slowed spiking, especially during depolarizing current injections. The two components of BK current in Purkinje somata likely contribute differently to spike repolarization and firing rate. Moreover, augmentation of BK current may partially underlie the action of EBIO and chlorzoxazone to alleviate disrupted Purkinje cell firing associated with genetic ataxias.