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Published: 14 March 2023

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1

Adair, Jeanette. "Alternate channel therapy for the pancreatic disease of Cystic Fibrosis." Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251005.

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2

Sharma, Aarushi. "HUMAN CLCA2 MODULATES THE CONDUCTANCE OF CALCIUM-ACTIVATED CHLORIDE CHANNELS BY REGULATION OF INTRACELLULAR CALCIUM." OpenSIUC, 2016. https://opensiuc.lib.siu.edu/dissertations/1252.

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Chloride channels play an essential role in the physiology of the respiratory system, the gastrointestinal tract, and secretory glands. Their dysregulation underlies debilitating pathologies such as cystic fibrosis, asthma, and certain cancers. The CLCA (Chloride Channel Accessory) gene family is thought to determine severity of these diseases by modulating an unidentified Calcium-activated Chloride Channel (CaCC). Recent evidence indicates Ano1 to be the mediator of strong quintessential calcium-activated chloride current in several cell types. Ano1 is highly expressed in airway epithelium and downregulated in cystic fibrosis patients. Human CLCA2 is also expressed in epithelium of airways and mammary glands, and there it promotes calcium-activated chloride current. Hence, we hypothesized that CLCA2 modulates the conductance of Ano1. We tested this by introducing Ano1 and CLCA2 together or separately into HEK293 cells, which express endogenous Ano1 at a low level. Using whole-cell voltage clamp, we found that CLCA2 enhanced the conductance of the endogenous CaCC. This current was inhibited by a specific inhibitor of Ano1, tannic acid. CLCA2 also increased both the amplitude and the onset rate of the Ano1-mediated current. To determine the mechanism by which CLCA2 amplifies Ano1 mediated current, we used co-immunoprecipitation with or without a protein cross-linking agent and to test whether the interaction if any, was stable or transient, respectively. Neither any interaction, nor any change in Ano1 multimerization was found. We next tested whether CLCA2 enhanced Ano1 conductance by increasing its stability or surface localization. Surface-labelling the cells expressing Ano1 alone or both proteins with biotin, no difference in Ano1 level or surface expression was detected. Ano1 has recently been shown to be activated by intracellular calcium released from endoplasmic reticulum (ER) stores and by subsequent store-operated calcium entry (SOCE). Therefore, we investigated whether CLCA2 could increase intracellular calcium levels. With Fluo-4 dye calcium imaging, we found that CLCA2 expression enhanced both ER calcium stores and SOCE upon exhaustion of intracellular stores, and the SOCE response could be abolished by a specific inhibitor of SOCE, BTP-2. This inhibitor also abolished CLCA2-induced chloride current, establishing that CLCA2 enhances CaCC via SOCE. Moreover, knockdown of CLCA2 in MCF10A cells, that naturally express both proteins, reduced both ER calcium stores and SOCE. Mutations that abolished the metalloprotease activity of CLCA2 or deleted the cytoplasmic tail had little effect on its enhancement of chloride current or intracellular calcium, suggesting that the uncleaved ectodomain was responsible for both effects of CLCA2. Since, the ectodomain is the most conserved region of the protein, we found that another member of the CLCA family, CLCA1, was also effective in enhancing intracellular calcium storage and SOCE. Co-immunoprecipitation studies further revealed that CLCA2 interacts in a ternary complex with mediators of SOCE, STIM1 and ORAI1. These results explain the CaCC-enhancing effects of CLCA family members and suggest a broader role in other calcium-dependent processes. Understanding the modulatory relationship between these molecules may lead to better therapies for airway diseases and Ano1-dependent cancers. Furthermore, the discovery that CLCA2 regulates intracellular calcium levels may explain its effects on cellular differentiation, stress response, and cell death.

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3

Brookfield, Rebecca. "The pharmacology and cardiovascular function of TMEM16A channels." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/the-pharmacology-and-cardiovascular-function-of-tmem16a-channels(bdc16466-cecd-4343-9d40-b20bc647d70f).html.

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Calcium-activated chloride channels (CaCCs) are ubiquitously expressed in a plethora of cell types and, consequently, are involved in numerous cellular processes as diverse as epithelial secretion, regulation of cardiac excitability and smooth muscle contraction. Current pharmacology of CaCCs is limited to compounds with low potency and poor selectivity. The lack of knowledge surrounding the molecular identity of the CaCC has greatly hindered the development of more specific drugs and has impaired our understanding of the channel physiology and biophysics. The recent discovery that the TMEM16A gene codes for CaCCs has offered hope for new developments in these areas. CaCCs have been suggested as possible targets to treat a variety of conditions including asthma as well as pulmonary and systemic hypertension. Due to the ubiquitous expression of CaCCs and the ability of the channel to interact with a number of pharmacological compounds with diverse chemical structures however, it was hypothesised that TMEM16A could be a possible source for off-target drug effects and may represent a concern for safety pharmacology. The principal aim of this thesis was to assess the functional significance of TMEM16A in the cardiovascular system, as this is one of the major systems of concern for safety pharmacology and accounts for the largest number of post-market drug withdrawals. The main findings of this study can be summarised as follows: 1) RT-PCR analysis revealed a ubiquitous expression of TMEM16A in tissues of the rat and human cardiovascular systems, including systemic and pulmonary arteries as well as cardiac tissue. Analysis also revealed the presence of multiple TMEM16A splice variants in all rat tissues examined, in addition to a number of other TMEM16x family members. 2) Myography experiments using the “classical” CaCC blocker niflumic acid and newly identified TMEM16A blockers confirmed a functional role for TMEM16A in phenylephrine-induced vascular smooth muscle contraction. 3) The suitability of currently available Cl- channel blockers for use as pharmacological tools for TMEM16A research was assessed using conventional whole-cell patch clamp and high-throughput electrophysiology techniques to respectively compare their potencies and selectivity over other cardiovascular ion channels. Of the compounds tested, DIDS and T16Ainh-A01 appeared the most suitable blockers; however all compounds had a degree of non-selectivity, raising concerns for their use in functional studies. In conclusion, these findings provide evidence for the ubiquitous expression and functional significance of TMEM16A within the cardiovascular system and support the hypothesis that TMEM16A is a concern for safety pharmacology and should be included into future pre-clinical safety assays. The inadequacy of current inhibitors however highlights the urgency for the development of novel potent and selective channel modulators for future TMEM16A research.

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4

Georgiou, Panayiotis Paulou. "Calcium-activated potassium-channels in mammalian eggs." Thesis, University of Edinburgh, 1985. http://hdl.handle.net/1842/29774.

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5

Farrington, Jasmine. "Calcium release activated calcium channels in human lung mast cells." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/6609/.

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6

Conrad, Rachel [Verfasser]. "Trafficking of voltage-activated calcium channels / Rachel Conrad." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2017. http://d-nb.info/1136717919/34.

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7

Millership, Joanne Ella. "Regulation and function of calcium-activated potassium channels." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503016.

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8

Marsey, Laura Louise. "Molecular and functional investigations of the calcium activated chloride channel in cystic fibrosis pancreatic duct cells." Thesis, University of East Anglia, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445193.

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9

Hagen, Brian M. "Regulation of calcium-activated potassium channels by localized calcium transients in murine colon." abstract and full text PDF (free order & download UNR users only), 2005. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3209955.

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10

D'hoedt, Dieter. "Structure-function analyses of small-conductance, calcium-activated potassium channels." Diss., [S.l.] : [s.n.], 2005. http://edoc.ub.uni-muenchen.de/archive/00006036.

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11

Lippiat, Jonathan David. "Molecular properties of recombinant large conductance calcium-activated potassium channels." Thesis, University of Leicester, 2001. http://hdl.handle.net/2381/29928.

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1. Currents through large conductance calcium-activated potassium channels were recorded using path clamp from human embryonic kidney (HEK) cells expressing recombinant DNA. 2. The permeation of potassium ions through single cloned rat channels, rSlo+1m was described using Eyring's rate theory. The model included two energy wells and three barriers. N-methyl-D-glucamine was found to block potassium permeation by binding to the intracellular binding site in the pore. 3. A HEK cell line was generated that stably expressed the human bladder BKCa channel subunit (hSlo). Macroscopic currents recorded from patches excised from these cells were activated by depolarisation and by intracellular calcium. The currents also exhibited a voltage- and calcium-dependent inactivation. This was shown to be due to block by contaminant levels of barium and a change in the potassium concentration gradient caused by the large potassium conductance. 4. A phenylalanine residue (F380) in the S6 transmembrane segment was mutated to both isoleucine and tyrosine. Both mutations reduced the unitary conductance and affected the gating of the channel. Mutating F380 to tyrosine enhanced channel opening states whilst mutating to isoleucine inhibited channel opening. 5. Searching EST databases for homologues of the BKCa channel subunit revealed new members. Human 1, 2, 3 and 4 subunits were cloned into bicistronic expression vectors for functional coexpression in HEK cells with the hSlo subunit. 6. The channels comprised of and the different subunits were characterised. The 1, 2 and 4 upregulated the BKCa channel activation kinetics and reduced the sensitivity of the channel to block by iberiotoxin. The 3 subunit had no noticeable effects on either kinetics or toxin block.

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12

Deng, Zhihui. "SMALL CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM (SK) CHANNELS IN MAMMALIAN SPINAL MOTONEURONS." Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1237821684.

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13

Bohm, Rudy Ashish. "Transcriptional control of slowpoke, a calcium activated potassium channel gene /." Full text (PDF) from UMI/Dissertation Abstracts International, 2000. http://wwwlib.umi.com/cr/utexas/fullcit?p3004218.

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14

Macdonald, Stephen Hsiao-Feng. "Alternative splicing of large-conductance calcium- and voltage-activated potassium (BK) channels." Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/29237.

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The aim of this thesis was to test the hypotheses that: i) alternative splicing may control subcellular localisation of BK channel α-subunits and ii) splice variants are differentially expressed in tissues, using the murine BK channel as the model system. To address whether alternative splice variants may be trafficked specifically to different subcellular compartments, epitope-tagged BK channel splice variants were expressed in a mammalian epithelial and endocrine cells. STREX and ZERO variants, in contrast to splice variant Δe23 that is C-terminally truncated, efficiently trafficked to the plasma membrane. Furthermore, splice variants can heteromultimerise in vivo. To investigate tissue specific distribution of splice variants, fluorogenic real time qRT-PCR assays were developed for five known BK channel alternative splice variants- ZERO, e20 (IYF), e21(STREX), e22, and Δe23 (TRUNC) at site C2 of splicing, and used to profile: i) the expression of these splice variants across various tissues in the adult mouse; ii) changes in ZERO and STREX variant expression in the mouse central nervous system during development and iii) STREX variant splicing in steroid responsive tissues of the stress axis. Splice variant expression patterns were distinct in different tissues with, for example, STREX expressed most highly in endocrine tissues and e22 in embryonic tissue. STREX variant expression was significantly reduced in the CNS across the period from embryo day 13 to postnatal day 35, possibly reflecting changes in cell excitability as development progresses and activity-dependent patterning of the CNS is completed. No significant changes in STREX expression were seen under various stress paradigms in adult mice. These data suggest that alternative pre-mRNA splicing is an important determinant of subcellular localisation and that tissues dynamically express a unique complement of BK channel splice variants to serve their physiological demands.

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15

Doorty, Kevina Bridget. "Identification of novel toxin inhibitors of apamin-sensitive calcium-activated potassium channels." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286597.

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16

McCartney, Claire Elizabeth. "Effect of hypoxia on neuronal large conductance calcium-activated potassium (BKca) channels." Thesis, University of Strathclyde, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410156.

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17

Clarke, Alison L. "Mechanism of Fatty Acid Modulation of Calcium-Activated Potassium Channel Activity." eScholarship@UMMS, 1997. http://escholarship.umassmed.edu/gsbs_diss/277.

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The purpose of this work was to determine whether the previously identified fatty acid activation of large conductance Ca2+-activated K+ (BK) channels from rabbit pulmonary artery smooth muscle cells was due to the direct interaction of the fatty acid with a site on the channel protein. If this was found to be the case, this study would also attempt to identify the site of fatty acid-protein interaction. Fatty acids released from membrane phospholipids by cellular phospholipases or available to the cell from the extracellular environment are important signaling molecules. Fatty acids can modulate the activity of a large number of molecules including protein kinases, phospholipases, adenylate and guanylate cyclases, G-proteins and ion channels. Fatty acids have also been shown to activate transcription of genes belonging to the steroid/thyroid superfamily of receptors. The actions of fatty acids on signal transduction pathways can be direct, whereby the fatty acid molecule itself is responsible for changes in the activity of enzymes, ion channels and other proteins. Alternatively, the effects of fatty acids may be indirect. In this case, biologically active lipids, produced from the metabolism of arachidonic acid are responsible for changes in cellular signaling. A previous study on the fatty acid modulation of rabbit pulmonary artery smooth muscle BK channel activity concluded that channel activation by fatty acids did not involve cycloxygenase, lip oxygenase and P450 metabolites (122), eliminating this indirect action of fatty acids as a possible mechanism. When dealing with the effects of fatty acids on membrane bound ion channel proteins, other mechanisms of action are also possible. For example, fatty acids are capable of entering the cell membrane and can thus affect properties of the lipid bilayer, such as membrane fluidity or membrane surface charge, that may consequently alter the activity of ion channel proteins. In addition, fatty acid mediated alterations of ion channel activity could result from the effect of fatty acids on ion channel associated proteins. To determine the mechanism of action of fatty acids on the activity of BK channels from rabbit pulmonary artery smooth muscle cells, all of the above mentioned mechanisms were considered. Most of the experiments described here were carried out using the patch-clamp technique and current recordings were performed in cell free, excised inside-out or outside-out membrane patches, in the absence of any added nucleotides and calcium. As a first step towards understanding how fatty acids modulate BK channel activity, as well as the type of protein site with which fatty acids may be interacting, we determined the structural features of the fatty acid molecule that are required for channel modulation. To do this the effects of a range of fatty acids and other lipids on BK channel activity were examined. The features required for BK channel activation were found to be the negatively charged head group and a carbon chain of greater than eight carbons. We also found that positively charged lipids produced the opposite effect of negatively charged lipids, a decrease in BK channel activity. A similar chain length requirement was also necessary for channel inhibition by positively charged lipids; short chain compounds did not alter activity while those with fourteen carbons or greater decreased activity. The identification of these required structural features suggested that a specific interaction between the charge on the lipid head group is required for channel modulation by these lipids. The requirement for a chain length of greater than eight carbons also suggests that a hydrophobic interaction is necessary for these lipids to be effective modulators of this channel. In addition, the identification of these required structural features makes it unlikely that modulation of BK channel activity by these lipid compounds is a consequence of a perturbation of the lipid environment in which the channel resides. Experiments were then carried out to determine whether modulation of BK channel activity by fatty acids and other charged lipids involved any of the following indirect mechanisms of action: 1) alterations in the concentration of calcium in the vicinity of the channel due to changes in membrane surface charge, or due to calcium stores attached to excised membrane patches, 2) alterations in the membrane electric field that the channel perceives due to changes in membrane surface charge and 3) changes in the activity of membrane bound protein kinases or protein phosphatases. In experiments where high ionic strength solutions were used to shield membrane surface charge, fatty acids and other charged lipids were still able to modulate BK channel activity suggesting that fatty acids do not act through a mechanism involving surface charge. Experiments carried out in high concentrations of EGTA (20 mM) make it unlikely that calcium is involved in the modulation of BK channels by fatty acids and other lipids. The involvement of membrane bound kinases or phosphatases is also unlikely as fatty acids effectively modulated BK channel activity in the presence of staurosporin, a kinase inhibitor, and okadaic acid, a phosphatase inhibitor. The elimination of these indirect and non-specific suggests that fatty acids and charged lipids modulate BK channel activity by directly interacting with, either the channel protein itself, or some other channel associated protein. To obtain further evidence that this indeed is the mechanism by which these lipids modulate BK channel activity; experiments were carried out to identify the site of action (i.e. side of the membrane) of both negatively and positively charged lipids. The negatively charged palmitoyl coenzyme A (PCoA) and a myristoylated positively charged peptide (myr-KPRPK), two compounds that are incapable of flipping across the bilayer, were used to identify the site of action of negatively and positively charged lipids. PCoA and myr-KPRPK produced their predicted effects of BK channel activation and suppression, respectively, only when they were applied to outside-out membrane patches. These experiments, therefore, support the contention that fatty acids and other charged lipids modulate BK channel activity by interacting with a site on the channel protein or a channel associated protein and that this site is found on the external membrane surface. If the site responsible for channel modulation by fatty acids and other charged lipids is contained within the BK channel protein itself, other members of this family may also possess this site, and thus be modulated by fatty acids. Experiments were performed, therefore, to determine whether the BK cloned channels, mslo, hslo and bslo could also be modulated by fatty acids. These cloned channels were expressed in the Xenopus oocytes, and whole-cell currents were recorded using the two-electrode voltage clamp technique. The fatty acids myristic and arachidonic acid were able to increase whole-cell current of oocytes expressing all clone types. The modulation of these cloned channels by fatty acids did not appear to involve calcium, the BK β-subunit or a bioactive metabolite of arachidonic acid. Although all possible mechanisms of action were not addressed in this study, the results support the idea that the site of fatty acid interaction resides in the channel protein itself. Taken together, therefore, these studies suggest that it is very likely that fatty acids and charged lipids modulate the activity of BK channels from smooth muscle cells of the rabbit pulmonary artery by directly interacting with an externally located site on the channel protein itself. The BK clones, mslo, hslo and bslo, are also modulated by fatty acids and it is likely that they share the same mechanism of action seen for BK channels from rabbit pulmonary artery smooth muscle cells.

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18

Matias, Madeleine Gundayao. "Animal calcium release-activated calcium (CRAC) channels are homologous and derived from the ubiquitous Cation Diffusion Facilitators." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p1453033.

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Thesis (M.S.)--University of California, San Diego, 2008.
Title from first page of PDF file (viewed June 25, 2008). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 48-51).

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19

Inglis, Victoria. "The effect of ã-dendrotoxin on calcium-activated potassium channels in neuroblastoma cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0008/MQ60131.pdf.

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20

Joshi, Atul. "A possible link between calmodulin and calcium-activated potassium channels in bovine chromaffin cells /." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=55663.

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21

Bahia, Parmvir Kaur. "A study of small and intermediate conductance calcium-activated potassium channels in sensory neurones." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445301/.

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The role of small and intermediate conductance calcium-activated potassium channels (SK and IK channels) in dorsal root ganglion (DRG) neurones was examined. Sixteen antibodies raised against human or rat SK/IK channel peptide epitopes were tested for their ability to stain cells expressing channel protein. Of sixteen antibodies, 12 (6 to SKI, 1 to SK2, 2 to SK3 and 3 to IK) were deemed suitable for immunohistochemistry in human or rat tissue. Real-time quantitative PCR (qPCR) of rat DRG cDNA was performed to examine SK/IK expression levels. DRG neurones produce mRNA for all SK/IK channels and these mRNA levels were found to increase during development. Antibody staining experiments using DRG neurones cultured from different aged animals produced a positive stain with the anti-SK3 antibody only. The number of cells that stained positively and the intensity of staining for SK3 increased with age. To investigate possible functional roles for SK/IK channels sensory neurones, action potential afterhyperpolarisations (AHPs) were recorded from cultured DRG and nodose cells. The majority of these AHPs proved to be insensitive to the SK channel blocker UCL 1848. Attempts to block medium duration AHPs in DRG cells using IK and calcium channel blockers, also failed in most cases, suggesting that some other potassium conductances) are responsible. The possibility that SK3 is functional at the terminals of primary afferents was examined next. Spinal cord slices stained with SK/EK channel antibodies revealed positive SK3 staining in the outer laminae of the dorsal horn, where small and large diameter DRG fibres are expected to terminate. In vivo experiments (done by Dr Rie Suzuki, Department of Pharmacology, UCL) using UCL 1848 and l-ethyl-2- benzimidazolinone (1-EBIO an SK channel opener) showed that SK channels are likely to be active at these terminals where they have a functional role in mediating innocuous mechanical and nociceptive responses.

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22

Chu, Benson. "Alcohol Modulation of N-methyl-D-aspartate Gated Receptor/Channels and Large Conductance Calcium-Activated Potassium Channels: a Dissertation." eScholarship@UMMS, 1998. http://escholarship.umassmed.edu/gsbs_diss/164.

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Clinically relevant concentrations of ethanol modulate the function of a number of ion channel proteins. A fundamental question regarding the effects of alcohol is whether the drug modifies ion channels by directly binding to the protein, indirectly by perturbing the surrounding membrane lipid, or some combination of both. This thesis further characterized ethanol's site of action by examining the effects of ethanol on N-methyl-D-aspartate (NMDA) receptor/channels and large conductance Ca2+-activated K+ (BK) channels at a number of levels using direct electrophysiological methods. In Chapter One, the magnitude of ethanol's inhibition of a number of cloned heteromeric NMDA receptor/channels in the absence or presence of a number of modulators was compared. The rank order of ethanol sensitivity for the subunit combinations studied was NR1b/NR2A > NR1b/NR2B > NR1b/NR2C > NR1b/NR2D. Modulation of the receptor with Mg2+, Zn2+, the glycine antagonist 7-Chlorokynurenic Acid, or after reduction or oxidation of the redox regulatory site did not alter the ethanol sensitivity of heteromeric NMDA receptors. Therefore, the ethanol sensitivity of NMDA receptor/channels is dependent upon which NR2 subunit is present, and ethanol's site of action is unrelated to these modulatory sites on the receptor/channel protein. In Chapter Two, ethanol's site of action at cloned BK channels was characterized using of a number of 1-alkanols. Ethanol, butanol, hexanol, and heptanol reversibly and dose-dependently increased the current carried through BK channels. Longer chain 1-alkanols, such as octanol had no effect on channels. In Chapter Three, the action of ethanol on BK channels reconstituted in a number of model planar bilayers was studied. Ethanol increased the activity of BK channels incorporated in bilayers composed of phosphatidylethanolamine (PE) and phosphatidylserine (PS) or PE alone by decreasing the average amount of time channels dwelled in the closed state. There was no significant effect of alcohol on either channel conductance or unitary current. Taken together, these data suggest that ethanol action on BK channels does not require the complex membrane architecture found in native membranes, and does not require freely diffusible cytoplasmic factors or proteins.

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23

Petrik, David. "The role of the ß4 subunit in phosphorylation of calcium-activated potassum [sic] channels a dissertation /." San Antonio : UTHSC, 2008. http://proquest.umi.com.libproxy.uthscsa.edu/pqdweb?did=1588771871&sid=3&Fmt=2&clientId=70986&RQT=309&VName=PQD.

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24

Sane, Mukta. "Role of Large Conductance, Calcium-Activated Potassium Channels (BKCa) in Vasorelaxation of Nitrate Tolerant Mesenteric Arteries." Diss., North Dakota State University, 2016. http://hdl.handle.net/10365/25665.

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25

Saqar, Wedad Ali. "Characterization of Small Conductance Calcium-Activated Potassium Channels in a Human Lens Epithelium Cell Line (B3)." Wright State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1401279427.

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26

Krishnamoorthy, Gayathri. "MECHANISM OF CALCIUM DEPENDENT GATING OF BKCa CHANNELS: RELATING PROTEIN STRUCTURE TO FUNCTION." online version, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1144444855.

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27

Murphy, Matthew M. "Investigating the Effects of CyPPA on Small-Conductance Calcium-Activated Potassium Channels in SOD1G93A Transgenic Mouse Model." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1589929963490428.

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28

Ro, Seungil. "SK channels : distribution, function and regulation in mouse colonic myocytes /." abstract and full text PDF (UNR users only), 2002. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3090879.

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29

Kye, Min-Jeong. "Regulation of small-conductance, calcium-activated potassium channels (SK) in mouse brain in response to aging and stress." [S.l.] : [s.n.], 2004. http://webdoc.sub.gwdg.de/diss/2004/kye/kye.pdf.

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30

Huston, Elaine. "Involvement of voltage activated calcium channels in neurotransmitter release and its modulation in cultured rat cerebellar granule neurones." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283291.

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31

Tjong, Yung-wui. "Mechanisms of attenuated large conductance calcium-activated potassium channel activity in rat hippocampal CA1 pyramidal neurons in chronic intermittent hypoxia." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B39793953.

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32

Hermann, David [Verfasser], and Andreas [Akademischer Betreuer] Draguhn. "Effects of Abeta Oligomers and State-Dependent Channel Blockers on High Voltage-Activated Calcium Channels / David Hermann ; Betreuer: Andreas Draguhn." Heidelberg : Universitätsbibliothek Heidelberg, 2013. http://d-nb.info/1177148390/34.

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33

Hillman, David James. "Membrane currents evoked by vasoactive compounds in vascular endothelial cells : contributions of small and intermediate conductance calcium-activated potassium channels." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445578/.

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The contribution of different calcium-activated potassium channel subtypes to agonist-evoked whole-cell currents was studied in cultured pig coronary artery endothelial cells. From a resting membrane potential of-5.9 0.5mV (n=102), 1-lOuM ATP, 1-1 OnM substance P and 1-lOOnM bradykinin hyperpolarised cell rafts to -50.7 1.6mV (n=76), -45.7 4.7mV (n=19) and -59.1 3.5mV (n=16), respectively. In small clusters of cells, 1 OuM ATP evoked outward currents which reversed close to EK and were sensitive to both the SKca channel blocker UCL 1848 (IC5o 1.2nM -65% maximal block) and the IKca/BKca channel blocker charybdotoxin (-85% block at 30-100nM). Surprisingly lOuM clotrimazole, a non selective blocker of IKca channels, abolished ATP-evoked currents in a total of three out of five cells. This requires further study. ImM 1-EBIO, which increases the calcium sensitivity of SKca and IKca channels, activated currents which were sensitive to lOOnM UCL 1848 and luM clotrimazole (blocked by 57.0 15.1% (n=3) and 89.0 1.6% (n=4), respectively). When applied in combination, these two blockers essentially abolished 1-EBIO evoked currents. Buffering intracellular calcium to 1.5uM activated outward currents which were sensitive to lOOnM UCL 1848, lOOnM charybdotoxin and lu.M clotrimazole (blocked by 28.3 5.4% (n=27), 101.2 0.5% (n=3), and 82.6 3.7% (n=22), respectively. Plasma membrane delimited expression of the SK3 channel protein was detected using fluorescence immunohistochemistry. In many vessels endothelium-derived hyperpolarising factor (EDHF)- mediated vasodilation is abolished by a combination of SKca and IKca channel blockers, which are frequently ineffective when applied alone. This has led some to suggest the existence of a novel channel with unusual pharmacology. The present study demonstrates, however, that separate SKca and IKca channels contribute to endothelial cell currents underlying the EDHF pathway. Based on protein expression and UCL 1848-sensitivity it is further proposed that the contributing SKca channels are formed of SK3 subunits.

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34

Shah, Yousef. "Effects of point mutations on the block of SK3 small-conductance calcium-activated potassium channels expressed in mammalian cell lines." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446491/.

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Small conductance calcium-activated K+ channels (SK channels) form a subfamily of K+ -selective, volt age-insensitive channels that have been recently cloned. This thesis is concerned primarily with an investigation of the pharmacology of these channels. Understanding their pharmacology is of potential clinical importance since SK channels participate in diverse physiological roles, for example, generating neuronal afterhyperpolarizations (that set tonic firing frequencies) and regulating smooth muscle contraction. This thesis consists of two parts. The first is concerned with expressing and establishing recording conditions for rSK3 in mammalian cell lines. This was made difficult because of channel run up and run down. However, some progress was made towards stabilizing channels through MgATP regulation and this allowed progress towards the second part (the major part) of this thesis; a functional characterization of site-directed point mutants that were created to better understand the pharmacology of these channels. First, two mutations were made to examine similarities between the pore structures of the KcsA and Shaker channels and the SK channels. The first of these mutants would be predicted to increase Tetraethylammonium (TEA) affinity to the sub-millimolar range, and the second to provide increased sensitivity to charybdotoxin (CTX) block. Both these predictions were fulfilled suggesting that the KcsA/Shaker pore structure can provide a reasonable model for the SK channel pore. However, an important difference was identified in the TEA sensitive mutant, indicating that although the channels are similar, they are not identical. Three UCL compounds were then studied; UCL 1848, UCL 1684, and UCL 1530 with six channel mutants. The effects of these mutations on blocker affinity provided the basis of a "map" of the channel residues interacting with UCL compounds and establishes that these blockers bind in the channel pore region. Further, experiments co-expressing wildtype (WT) and mutant subunits demonstrate that UCL compounds do not require all four "sensitive" subunits for block, suggesting an asymmetric interaction with the channel outer pore. Finally, some work has also been done to define the possible assembly patterns of SK subunits in forming heteromeric channels. Evidence is presented that SKI and SK3 can co-assemble. Overall, this thesis provides a starting point for understanding the pharmacology of small molecule SK channel blockers at the molecular level.

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35

Holland, Michael. "A patch clamp study of pharmacological and physiological regulators of large conductance calcium-activated potassium channels in arterial smooth muscle cells." Thesis, University of Leicester, 1997. http://hdl.handle.net/2381/29937.

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In the 1980s a group of vasodilator drugs were found to possess a common mechanism which involved opening KATP channels located in the cell membrane of smooth muscle cells, leading to vasorelaxation via membrane hyperpolarisation. A number of additional K+ channels have been identified in vascular smooth muscle cells and one of these channels, the large conductance calcium-activated K+ channel (BKCa), is a promising therapeutic target.;This thesis uses the various configurations of the patch-clamp technique to examine the effects of NS1619, nitric oxide (NO) and compounds resulting from the activation of the cGMP signalling pathway by NO, on the activity of ion channels.;Using single smooth muscle cells enzymatically isolated from the rat basilar artery, NS1619 was confirmed as an effective BKCa channel opener and hyperpolarising agent. Studies of the mechanism of action of NS1619 concluded that it has a direct effect on the BKCa channel itself or an associated regulatory site, possibly leading to an increase in the Ca2+-sensitivity of the BKCa channel. NS1619 also blocked at least two other channels, voltage-activated K+ channels and DHP-sensitive Ca2+ channels, and this latter effect almost certainly explains the functional vasorelaxation produced by NS1619 actions which will certainly limit the use of NS1619 in defining physiological roles for BKCa channels.;Nitric oxide activated whole cell currents when applied to single smooth muscle cells, which were blocked by specific BKCa channel blockers. Additional experiments determined that this action of NO could not be explained by a direct effect on BKCa channels but probably occurred by a mechanism involving a phosphorylation reaction catalysed by cGMP-dependent protein kinase. This stimulatory effect of cGMP-dependent protein kinase on BKCa channels may be involved in the vasorelaxation produced by nitric oxide and nitrovasodilators.

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36

Braxton, Joi Requan. "Effect of preload on the response of mouse trachea smooth muscle to cholinergic stimulation a thesis /." San Antonio : UTHSC, 2008. http://learningobjects.library.uthscsa.edu/cdm4/item_viewer.php?CISOROOT=/theses&CISOPTR=33&CISOBOX=1&REC=10.

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37

Degen, Rudolf [Verfasser], Marc [Akademischer Betreuer] Spehr, and Ivan [Akademischer Betreuer] Manzini. "Identification and physiological characterization of calcium-activated ion channels in vomeronasal sensory neurons of the mouse / Rudolf Degen ; Marc Spehr, Ivan Manzini." Aachen : Universitätsbibliothek der RWTH Aachen, 2021. http://d-nb.info/1238693865/34.

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38

Tharp, Darla L. "Role of the intermediate-conductance Ca²⁺-activated K⁺ channel (K[ca]3.1) in coronary smooth muscle cell phenotypic modulation." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/5936.

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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.
The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "December 2007" Includes bibliographical references.

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39

Apolinar, Sanrda. "BK channel involvement in beta-adrenergic relaxation of murine tracheal smooth muscle a thesis /." San Antonio : UTHSC, 2008. http://learningobjects.library.uthscsa.edu/cdm4/item_viewer.php?CISOROOT=/theses&CISOPTR=32&CISOBOX=1&REC=3.

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40

Wynne, Patricia M. "Ethanol Sensitivity and Tolerance of Rat Neuronal BK Channels: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/399.

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BK channels are well studied targets of acute ethanol action. They play a prominent role in neuronal excitability and have been shown to play a significant role in behavioral ethanol tolerance in invertebrates. The focus of my work centers on the effects of alcohol on the BK channel and comprises studies that examine how subcellular location affects acute ethanol sensitivity and how duration of acute alcohol exposure impacts the development of rapid tolerance. My results also provide potential mechanisms which underlie acute sensitivity and rapid tolerance. I first explore BK channel sensitivity to ethanol in the three compartments (dendrite, cell body, and nerve terminal) of magnocellular neurons in the rat hypothalamic-neurohypophysial (HNS) system. The HNS system provides a particularly powerful preparation in which to study the distribution and regional properties of ion channel proteins because the cell bodies are physically separated from the nerve terminals. Using electrophysiological and immunohistochemical techniques I characterize the BK channel in each of the three primary compartments and find that dendritic BK channels, similar to somatic channels, but in contrast to nerve terminal channels, are insensitive to alcohol. Furthermore, the gating kinetics, calcium sensitivity, and iberiotoxin sensitivity of channels in the dendrite are similar to somatic channels but sharply contrast terminal channels. The biophysical and pharmacological properties of somatodendritic vs. nerve terminal channels are consistent with the characteristics of exogenously expressed αβ1 vs. αβ4 channels, respectively. Therefore, one possible explanation for my findings is a selective distribution of β1 subunits to the somatodendritic compartment and β4 subunits to the terminal compartment. This hypothesis is supported immunohistochemically by the appearance of distinct punctate β1 or β4 channel clusters in the membrane of somatodendritic or nerve terminal compartments, respectively. In conclusion, I found that alcohol sensitivity of BK channels within the HNS system is dependent on subcellular location and postulate that β-subunits modulate ethanol sensitivity of HNS BK channels. In the second and primary focus of my thesis I explore tolerance development in the striatum, a brain region heavily implicated in addiction. Numerous studies have demonstrated that duration of drug exposure influences tolerance development and drug dependence. To further elucidate the mechanisms underlying behavioral tolerance I examined if BK channel tolerance was dependent on duration of alcohol exposure using patch clamp techniques in cultured striatal neurons from P8 rats. I found that persistence of rapid tolerance is indeed a function of exposure time and find it lasts surprisingly long. For example, after a 6 hr exposure to 20 mM ethanol, acute sensitivity was still suppressed at 24 hrs withdrawal. However, after a 1 or 3 hr exposure period, sensitivity had returned after only 4 hrs. I also found that during withdrawal from a 6 hr but not a 3 hr exposure the biophysical properties of BK channels change and that this change is correlated with an increase in mRNA levels of the alcohol insensitive STREX splice variant. Furthermore, BK channel properties during withdrawal from a 6 hr exposure to alcohol closely parallel the properties of STREX channels exogenously expressed in HEK293 cells. In conclusion I have established that BK channels develop rapid tolerance in striatal neurons, that rapid tolerance is dependent upon exposure protocol, and is surprisingly persistent. These findings present another mechanism underlying BK channel tolerance and possibly behavioral tolerance. Since these phenomena are dependent on duration of drug exposure my results may find relevance in explaining how drinking patterns impact the development of alcohol dependence in humans.

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Feinberg-Zadek, Paula Leslie. "Alcohol Modulation of Human BK Channels Evidence for β-Subunit Dependent Plasticity in Functional Ethanol Tolerance: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/195.

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Alcoholism is responsible for more than 6% of deaths internationally per annum. The development of acute tolerance to ethanol (EtOH) is a critical component of alcoholism. Previous studies identified large conductance calcium-activated potassium (BK) channels as potential EtOH targets in a variety of species and cells. In order to elucidate mechanisms underlying tolerance development, I used inside-out patch clamp techniques to measure EtOH induced changes in channel activity (measured as open probability) of hSlo, hSlo+β1, and hSlo+β4 channels exogenously expressed in HEK 293 cells. I show that the human BK channels have subunit dependent responses to acute application of EtOH, and the magnitude of potentiation was dependent on the concentration of ethanol used and the type of β-subunit expressed. In addition the subunit dependent effects on the channels were a function of cytosolic calcium concentration. Furthermore, to determine if BK channels in ripped-off patches can become tolerant to EtOH, I monitored changes in channel activity in response to a second application of the drug, 10-minutes after washing-out the first exposure. I found that channels were less responsive to the second exposure, indicative of tolerance. I examined long-term consequences of EtOH exposure by repeating these experiments on cells cultured in 25 mM EtOH in the culture medium for 24-hours. Under these conditions, all three channel types show chronic tolerance has developed as revealed by the response to acute EtOH applications. Subunit-dependent differences to the development of acute tolerance were apparent, however. In response to a second application to EtOH, hSlo+β4 channels were now inhibited. Overall, these results indicate that BK channels respond to and develop tolerance to EtOH in the absence of cellular context, suggesting the possibility that alcohol tolerance within organisms may be in part mediated by changes imparted by EtOH on BK channels directly.

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42

Assadian, Sarah. "Rodent FDG-PET imaging for the pre-clinical assessment of novel glioma therapies." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101836.

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The rapid discovery of novel therapeutic agents, targeting the specific mechanism of cancer progression, invasion and angiogenesis, necessitates the development and validation of efficient techniques to assess the therapeutic efficacy of these drugs in vivo. Recently the development of dedicated PET scanners for the imaging of small animals, such as the microPET system (CTI Concorde R4), has allowed for the high-resolution functional and molecular imaging of murine and rodent models of disease. This study, investigates the ability of microPET imaging, using the 18F labelled 2-fluoro-2-deoxyglucose (FDG) PET tracer, to detect the therapeutic efficacy of novel targeted therapies in a rat model of glioma. This technique potentially allows for the rapid and high-throughput assessment of tumour response and evaluation of efficacy of such therapeutic agents in vivo at the pre-clinical stage and will, consequently, facilitate the translation of these novel drugs from the discovery to the clinical phases.
La découverte accélérée de nouvelles molécules thérapeutiques qui ciblent lesmécanismes de progression du cancer tels que l'invasion et l'angiogenèse, nécessite lamise au point et la validation de techniques efficaces qui permettent d'évaluer l'efficacitéthérapeutique de ces agents in vivo. Le développement récent des scanners detomographie à émission de positron (TEP) dédiés à l'imagerie de petits animaux(microPET, CT! Concorde R4), permet aujourd'hui d'obtenir une image fonctionnelle etmoléculaire de haute résolution des modèles rongeurs. Cette étude s'intéresse au potentieldu 18F-2-fluoro-2-deoxyglucose (FDG) en utilisant l'imagerie microPET dansl'évaluation de l'efficacité de nouveaux agents thérapeutiques dans un modèle de gliomechez le. rat. Cette technique pourrait éventuellement mener à une évaluation rapide et àgrande échelle de la réponse tumorale, ainsi que la mesure de l'efficacité d'agentsthérapeutiques in vivo au stade d'étude préclinique. Globalement, cette étude a pour butde faciliter la transition entre la découverte de nouvelles molécules thérapeutiques et leursapplications cliniques.

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43

Waiczies, Sonia. "Modulation of human antigen-specific T-cell response therapeutic implications for multiple sclerosis /." Doctoral thesis, [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969681844.

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44

Herr, Julia Emily. "Mechanisms of Rupture of Mucin Vesicles from the Slime of Pacific Hagfish (Eptatretus stoutii): Roles of Inorganic Ions and Aquaporin Water Channels." Thesis, 2012. http://hdl.handle.net/10214/3687.

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Pacific hagfish (Eptatretus stoutii) slime mucin vesicles are released by holocrine secretion with membranes that remain intact until the vesicle contacts seawater and ruptures. This thesis is an investigation of the mechanisms that drive mucin vesicle rupture for mucin release. Using isolated mucin vesicles collected from the slime glands of the hagfish, I tested the effects of a variety of solutions and drugs on vesicle rupture. I found that there are two categories of mucin vesicle that differ in their sensitivity to calcium ions, and that calcium-dependent vesicle rupture was inhibited with anion channel inhibitors. I also found that vesicle swelling rate was reduced by the aquaporin inhibitor mercuric chloride. Together, these data suggest that mucin vesicle rupture is partially dependent on the movement of chloride ions from seawater through calcium-activated anion channels and the rapid influx of water through aquaporin-like proteins in the vesicle membrane.
NSERC Discovery Grant, NSERC CGSM scholarship, Canada Foundation for Innovation, Ontario Ministry of Research and Innovation

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45

Leverköhne, Ina [Verfasser]. "The novel CLCA gene family of multifunctional calcium-activated chloride channels : genetic, structural and expression studies in the murine model system / by Ina Leverköhne." 2003. http://d-nb.info/969346182/34.

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46

Gao, Yadong [Verfasser]. "The role of calcium-activated potassium channels and store-operated calcium channels in human macrophages / vorgelegt von Yadong Gao." 2007. http://d-nb.info/986359440/34.

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47

D'hoedt, Dieter [Verfasser]. "Structure-function analyses of small-conductance, calcium-activated potassium channels / Dieter D'hoedt." 2005. http://d-nb.info/982304323/34.

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48

"Functional expression of sperm Ca²⁽-activated K⁽ channels in xenopus oocytes and their modulations by Ca²⁽-evoking agonists." 2000. http://library.cuhk.edu.hk/record=b6073247.

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by So Siu Cheung, Eddie.
"September 2000."
Thesis (Ph.D.)--Chinese University of Hong Kong, 2000.
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.

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49

Wang, Ya-Jean, and 王雅貞. "Stimulatory Effects of the Estrogen-Receptor Modulators on Large-Conductance Calcium-Activated Potassium Channels." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/13761727049091187819.

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博士
國立成功大學
基礎醫學研究所
96
The large conductance Ca2+-activated K+ (BKCa) channels, which are formed by ��-subunit tetramers, are encoded by a nearly ubiquitous, alternatively spliced gene, SLO (KCNMA1). Activation of the channel is under dual control, i.e., allosterically switched on either by membrane depolarization or by increased [Ca2+]i. Recent studies demonstrated that in addition to their binding to estrogen receptors, the modulators of estrogen receptors (ERs) may have direct effects on the activity of these channels in a non-genomic pathway. In these studies, a series of compounds known to bind to ERs were investigated concerning their possible effects on ion currents. First, diosgenin (3��-hydroxy-5-spirostene), originally extracted from the root of wild yam (Dioscorea villosa), was reported to antagonize the binding of estradiol to ERs. The results of this study provide the evidence that it can activate BKCa channels in HCN-1A neuronal cells through increased [Ca2+]i. Second, resveratrol (trans-3,4',5-trihydroxystilbene) is a common phytoalexin that was found in some edible materials, including grape skins, peanuts, and red wine. Several lines of evidence suggest that resveratrol may exert protective effects on the cardiovascular system. Our results also demonstrated that this compound can directly stimulate the activity of BKCa channel in human cardiac fibroblasts (HCFs). It is likely that the observed increase in activity of BKCa channels by resveratrol is due to its stimulation of the probability of channel openings which occurred in rapid open-close transitions. However, no modification in single-channel conductance of BKCa channels was found. Third, PPT (4,4′,4′′-(4-propyl-[1H]-pyrazole-1,3,5-triyl) tris-phenol) and DPN (2,3-bis(4-hydroxyphenyl)-propionitrile) were ER agonists selective for ER-�� and ER-β, respectively. PPT or DPN applied to the intracellular face of the membrane enhanced the activity of BKCa channels with no change in single-channel conductance. PPT- and DPN-stimulated increase in BKCa channels revealed novel pharmacological properties attributable to the activity of these channels, and their direct increase in BKCa-channels activity may contribute to cellular function. Finally, the theoretical simulations were used to predict effection of action potential duration by alterations in the BKCa channel conductance. The increase of BKCa channel conductance may reduce cardiac action potential duration. Resveratrol (or DPN) induced stimulation of BKCa channels may regulate cardiac action potential. Prolongation of action potential in electrically coupled cardiomyocytes can be reversed by increase of BKCa channel activity. Taken together, the regulation by ER modulators of BKCa-channel activity in a variety of cells can be due to a mechanism unlinked to their binding to ERs. These modulators of the channels may provide a therapeutic potential in neurological disorders and cardiovascular disease.

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50

"High voltage activated calcium channels in pancreatic beta-cells: Possible role in glucose desensitization." Tulane University, 2005.

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Glucose desensitization is a common phenomenon that is associated with a glucose induced reduction in insulin secretion in pancreatic beta-cells. The exact mechanism behind this event is currently unknown. It has been suggested that desensitization involves overstimulation that is related to abnormal maintenance of basal calcium in pancreatic beta-cells. However, the mechanism behind this alteration in basal calcium is unknown. In our study we wanted to first determine the level of expression of the major HVA calcium channels in beta-cells. We found that INS-1 and rat pancreatic beta-cells express L-type (alpha1C & alpha1D), N-type, and P/Q-type calcium channels. We also show that these channels are functionally expressed and can contribute to calcium influx, but only L- and N-type are involved with insulin secretion. We also found that chronic glucose increases basal calcium in beta-cells and that the increase in calcium partially involves LVA calcium channels, suggesting overstimulation is responsible for increased calcium. It was also found that increased basal calcium was associated with attenuated HVA calcium influx. Additionally, we found that chronic elevated glucose decreases gene expression of the channels involved with insulin secretion. We then wanted to test if increased calcium was capable of regulating calcium channel migration directly. We found that N- and L-channels exhibit significant increases in current when intracellular calcium is chelated, suggesting that these channels may be recruited to the plasma membrane under this condition. Using cytoskeleton mediators, we found that increased current indeed involves cellular machinery that may be associated with channel migration. We were able to visualize that changes in basal calcium induce channel migration using immunofluorescence and Western blot analysis. Taken together, these data suggest that glucose induced changes in calcium may regulate the HVA calcium channels involved with insulin secretion
acase@tulane.edu

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