Journal articles: 'C-type inactivation'

1

Villalba-Galea, Carlos A., Takeharu Kawano, and Diomedes E. Logothetis. "C-Type Inactivation in KV2.1 Channels." Biophysical Journal 116, no. 3 (February 2019): 15a. http://dx.doi.org/10.1016/j.bpj.2018.11.122.

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Yan, Jiusheng, Qin Li, and Richard W. Aldrich. "Closed state-coupled C-type inactivation in BK channels." Proceedings of the National Academy of Sciences 113, no. 25 (June 13, 2016): 6991–96. http://dx.doi.org/10.1073/pnas.1607584113.

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Ion channels regulate ion flow by opening and closing their pore gates. K+ channels commonly possess two pore gates, one at the intracellular end for fast channel activation/deactivation and the other at the selectivity filter for slow C-type inactivation/recovery. The large-conductance calcium-activated potassium (BK) channel lacks a classic intracellular bundle-crossing activation gate and normally show no C-type inactivation. We hypothesized that the BK channel’s activation gate may spatially overlap or coexist with the C-type inactivation gate at or near the selectivity filter. We induced C-type inactivation in BK channels and studied the relationship between activation/deactivation and C-type inactivation/recovery. We observed prominent slow C-type inactivation/recovery in BK channels by an extreme low concentration of extracellular K+ together with a Y294E/K/Q/S or Y279F mutation whose equivalent in Shaker channels (T449E/K/D/Q/S or W434F) caused a greatly accelerated rate of C-type inactivation or constitutive C-inactivation. C-type inactivation in most K+ channels occurs upon sustained membrane depolarization or channel opening and then recovers during hyperpolarized membrane potentials or channel closure. However, we found that the BK channel C-type inactivation occurred during hyperpolarized membrane potentials or with decreased intracellular calcium ([Ca2+]i) and recovered with depolarized membrane potentials or elevated [Ca2+]i. Constitutively open mutation prevented BK channels from C-type inactivation. We concluded that BK channel C-type inactivation is closed state-dependent and that its extents and rates inversely correlate with channel-open probability. Because C-type inactivation can involve multiple conformational changes at the selectivity filter, we propose that the BK channel’s normal closing may represent an early conformational stage of C-type inactivation.

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3

Li, Xiaoyan, Glenna C. L. Bett, Xuejun Jiang, Vladimir E. Bondarenko, Michael J. Morales, and Randall L. Rasmusson. "Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication." American Journal of Physiology-Heart and Circulatory Physiology 284, no. 1 (January 1, 2003): H71—H80. http://dx.doi.org/10.1152/ajpheart.00392.2002.

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Kv1.4 encodes a slowly recovering transient outward current ( I to), which inactivates by a fast N-type (intracellular ball and chain) mechanism but has slow recovery due to C-type inactivation. C-type inactivation of the NH2-terminal deletion mutant (fKv1.4ΔN) was inhibited by 98 mM extracellular K+concentration ([K+]o), whereas N-type was unaffected. In 98 mM [K+]o, removal of intracellular K+ concentration ([K+]i) speeded C-type inactivation but had no effect on N-type inactivation, suggesting that C-type inactivation is sensitive to K+ binding to intracellular sites. C-type inactivation is thought to involve closure of the extracellular pore mouth. However, a valine to alanine mutation on the intracellular side of S6 (V561A) of fKv1.4ΔN alters recovery and results in anomalous speeding of C-type inactivation with increasing [K+]o. Extracellular pH (pHo) modulated both N- and C-type inactivation through an S5-H5 linker histidine (H508) with acidosis speeding both N- and C-type inactivation. Mutation of an extracellular lysine to a tyrosine (K532Y) slowed C-type inactivation and inhibited the pH dependence of both N- and C-type inactivation. These results suggest that mutations, [K+], and pH modulate inactivation through membrane-spanning mechanisms involving S6.

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4

Kurata, Harley T., Zhuren Wang, and David Fedida. "NH2-terminal Inactivation Peptide Binding to C-type–inactivated Kv Channels." Journal of General Physiology 123, no. 5 (April 12, 2004): 505–20. http://dx.doi.org/10.1085/jgp.200308956.

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In many voltage-gated K+ channels, N-type inactivation significantly accelerates the onset of C-type inactivation, but effects on recovery from inactivation are small or absent. We have exploited the Na+ permeability of C-type–inactivated K+ channels to characterize a strong interaction between the inactivation peptide of Kv1.4 and the C-type–inactivated state of Kv1.4 and Kv1.5. The presence of the Kv1.4 inactivation peptide results in a slower decay of the Na+ tail currents normally observed through C-type–inactivated channels, an effective blockade of the peak Na+ tail current, and also a delay of the peak tail current. These effects are mimicked by addition of quaternary ammonium ions to the pipette-filling solution. These observations support a common mechanism of action of the inactivation peptide and intracellular quaternary ammonium ions, and also demonstrate that the Kv channel inner vestibule is cytosolically exposed before and after the onset of C-type inactivation. We have also examined the process of N-type inactivation under conditions where C-type inactivation is removed, to compare the interaction of the inactivation peptide with open and C-type–inactivated channels. In C-type–deficient forms of Kv1.4 or Kv1.5 channels, the Kv1.4 inactivation ball behaves like an open channel blocker, and the resultant slowing of deactivation tail currents is considerably weaker than observed in C-type–inactivated channels. We present a kinetic model that duplicates the effects of the inactivation peptide on the slow Na+ tail of C-type–inactivated channels. Stable binding between the inactivation peptide and the C-type–inactivated state results in slower current decay, and a reduction of the Na+ tail current magnitude, due to slower transition of channels through the Na+-permeable states traversed during recovery from inactivation.

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Claydon, T. W., M. R. Boyett, A. Sivaprasadarao, and C. H. Orchard. "Two pore residues mediate acidosis-induced enhancement of C-type inactivation of the Kv1.4 K+ channel." American Journal of Physiology-Cell Physiology 283, no. 4 (October 1, 2002): C1114—C1121. http://dx.doi.org/10.1152/ajpcell.00542.2001.

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Acidosis inhibits current through the Kv1.4 K+ channel, perhaps as a result of enhancement of C-type inactivation. The mechanism of action of acidosis on C-type inactivation has been studied. A mutant Kv1.4 channel that lacks N-type inactivation (fKv1.4 Δ2–146) was expressed in Xenopus oocytes, and currents were recorded using two-microelectrode voltage clamp. Acidosis increased fKv1.4 Δ2–146 C-type inactivation. Replacement of a pore histidine with cysteine (H508C) abolished the increase. Application of positively charged thiol-specific methanethiosulfonate to fKv1.4 Δ2–146 H508C increased C-type inactivation, mimicking the effect of acidosis. Replacement of a pore lysine with cysteine (K532C) abolished the acidosis-induced increase of C-type inactivation. A model of the Kv1.4 pore, based on the crystal structure of KcsA, shows that H508 and K532 lie close together. It is suggested that the acidosis-induced increase of C-type inactivation involves the charge on H508 and K532.

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6

Starkus, John G., Lioba Kuschel, Martin D. Rayner, and Stefan H. Heinemann. "Ion Conduction through C-Type Inactivated Shaker Channels." Journal of General Physiology 110, no. 5 (November 1, 1997): 539–50. http://dx.doi.org/10.1085/jgp.110.5.539.

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C-type inactivation of Shaker potassium channels involves entry into a state (or states) in which the inactivated channels appear nonconducting in physiological solutions. However, when Shaker channels, from which fast N-type inactivation has been removed by NH2-terminal deletions, are expressed in Xenopus oocytes and evaluated in inside-out patches, complete removal of K+ ions from the internal solution exposes conduction of Na+ and Li+ in C-type inactivated conformational states. The present paper uses this observation to investigate the properties of ion conduction through C-type inactivated channel states, and demonstrates that both activation and deactivation can occur in C-type states, although with slower than normal kinetics. Channels in the C-type states appear “inactivated” (i.e., nonconducting) in physiological solutions due to the summation of two separate effects: first, internal K+ ions prevent Na+ ions from permeating through the channel; second, C-type inactivation greatly reduces the permeability of K+ relative to the permeability of Na+, thus altering the ion selectivity of the channel.

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7

Trefilov, B. B., N. V. Nikitina, and I. K. Leonov. "THE KINETICS OF THE INACTIVATION OF THE HEPATITIS VIRUS TYPE I (AVIHEPATOVIRUS, PICORNAVIRIDAE)." Problems of Virology, Russian journal 63, no. 3 (June 20, 2018): 135–38. http://dx.doi.org/10.18821/0507-4088-2018-63-3-135-138.

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Experimental data on the kinetics of the inactivation of the vaccine strain of the duckling hepatitis virus of the type I with increased temperature and aminoethyl ethylenimine are presented. It was shown that the vaccine strain 3M-UNIIP of the hepatitis virus of ducklings of type I was comparatively thermostable at 56°C and sensitive to the action of aminoethyl ethylenimine; the time of complete inactivation of the virus at a final concentration of 0.1% at 37°C was 24 h. The obtained results suggest that aminoethyl ethylenimine can be used as an inactivator in manufacturing inactivated vaccine against viral hepatitis of ducklings of type I.

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8

Mathes, Chris, Joshua J. C. Rosenthal, Clay M. Armstrong, and William F. Gilly. "Fast Inactivation of Delayed Rectifier K Conductance in Squid Giant Axon and Its Cell Bodies." Journal of General Physiology 109, no. 4 (April 1, 1997): 435–48. http://dx.doi.org/10.1085/jgp.109.4.435.

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Inactivation of delayed rectifier K conductance (gK) was studied in squid giant axons and in the somata of giant fiber lobe (GFL) neurons. Axon measurements were made with an axial wire voltage clamp by pulsing to VK (∼−10 mV in 50–70 mM external K) for a variable time and then assaying available gK with a strong, brief test pulse. GFL cells were studied with whole-cell patch clamp using the same prepulse procedure as well as with long depolarizations. Under our experimental conditions (12–18°C, 4 mM internal MgATP) a large fraction of gK inactivates within 250 ms at −10 mV in both cell bodies and axons, although inactivation tends to be more complete in cell bodies. Inactivation in both preparations shows two kinetic components. The faster component is more temperature-sensitive and becomes very prominent above 12°C. Contribution of the fast component to inactivation shows a similar voltage dependence to that of gK, suggesting a strong coupling of this inactivation path to the open state. Omission of internal MgATP or application of internal protease reduces the amount of fast inactivation. High external K decreases the amount of rapidly inactivating IK but does not greatly alter inactivation kinetics. Neither external nor internal tetraethylammonium has a marked effect on inactivation kinetics. Squid delayed rectifier K channels in GFL cell bodies and giant axons thus share complex fast inactivation properties that do not closely resemble those associated with either C-type or N-type inactivation of cloned Kv1 channels studied in heterologous expression systems.

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9

Biagi, B. A., and J. J. Enyeart. "Multiple calcium currents in a thyroid C-cell line: biophysical properties and pharmacology." American Journal of Physiology-Cell Physiology 260, no. 6 (June 1, 1991): C1253—C1263. http://dx.doi.org/10.1152/ajpcell.1991.260.6.c1253.

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The whole cell version of the patch-clamp technique was used to characterize voltage-gated Ca2+ channels in the calcitonin-secreting rat thyroid C-cell line 6-23 (clone 6). Three types of Ca2+ channels could be distinguished based on differences in voltage dependence, kinetics, and pharmacological sensitivity. T-type current was half-maximal at -31 mV, showed steady-state voltage-dependent inactivation that was half-maximal at -57 mV, inactivated with a voltage-dependent time constant that reached a minimum of 20 ms at potentials positive to -20 mV, and deactivated with a single time constant of approximately 2 ms at -80 mV. Reactivation of inactivated channels occurred with a time constant of 1.26 s at -90 mV. T current was selectively blocked by Ni2+ at concentrations between 5 and 50 microM. La3+ and Y3+ blocked the T current at 10- to 20-fold lower concentrations. Dihydropyridine-sensitive L-type current was half-maximal at a test potential of -3 mV and was approximately doubled in size when Ba2+ replaced Ca2+ as the charge carrier. Unlike L-type Ca2+ current in many cells, this current in C-cells displayed little Ca(2+)-dependent inactivation. N-type current was composed of inactivating and sustained components that were inhibited by omega-conotoxin. The inactivating component was half-maximal at +9 mV and could be fitted by two exponentials with time constants of 22 and 142 ms. A slow inactivation of N current with a time constant of 24.9 s was observed upon switching the holding potential from -80 to -40 mV. These results demonstrate that, similar to other neural crest derived cells, thyroid C-cells express multiple Ca2+ channels, including one previously observed only in neurons.

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10

Shimizu, H., K. Yamada, and S. Oiki. "An ion binding site competing with C-type inactivation." Seibutsu Butsuri 41, supplement (2001): S214. http://dx.doi.org/10.2142/biophys.41.s214_1.

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11

Cuello, Luis G., Vishwanath Jogini, D. Marien Cortes, and Eduardo Perozo. "Structural mechanism of C-type inactivation in K+ channels." Nature 466, no. 7303 (July 2010): 203–8. http://dx.doi.org/10.1038/nature09153.

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12

Hoshi, Toshinori, Wonpil Im, and Clay M. Armstrong. "Pore Dilation in C-Type Inactivation of Potassium Channels." Biophysical Journal 98, no. 3 (January 2010): 522a. http://dx.doi.org/10.1016/j.bpj.2009.12.2836.

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13

Yan, Jiusheng, Wei Wang, and Richard W. Aldrich. "Closed State Coupled C-Type Inactivation in BK Channels." Biophysical Journal 106, no. 2 (January 2014): 642a. http://dx.doi.org/10.1016/j.bpj.2013.11.3554.

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14

Ogielska, Eva M., and Richard W. Aldrich. "Functional Consequences of a Decreased Potassium Affinity in a Potassium Channel Pore." Journal of General Physiology 113, no. 2 (February 1, 1999): 347–58. http://dx.doi.org/10.1085/jgp.113.2.347.

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Ions bound near the external mouth of the potassium channel pore impede the C-type inactivation conformational change (Lopez-Barneo, J., T. Hoshi, S. Heinemann, and R. Aldrich. 1993. Receptors Channels. 1:61– 71; Baukrowitz, T., and G. Yellen. 1995. Neuron. 15:951–960). In this study, we present evidence that the occupancy of the C-type inactivation modulatory site by permeant ions is not solely dependent on its intrinsic affinity, but is also a function of the relative affinities of the neighboring sites in the potassium channel pore. The A463C mutation in the S6 region of Shaker decreases the affinity of an internal ion binding site in the pore (Ogielska, E.M., and R.W. Aldrich, 1998). However, we have found that this mutation also decreases the C-type inactivation rate of the channel. Our studies indicate that the C-type inactivation effects observed with substitutions at position A463 most likely result from changes in the pore occupancy of the channel, rather than a change in the C-type inactivation conformational change. We have found that a decrease in the potassium affinity of the internal ion binding site in the pore results in lowered (electrostatic) interactions among ions in the pore and as a result prolongs the time an ion remains bound at the external C-type inactivation site. We also present evidence that the C-type inactivation constriction is quite local and does not involve a general collapse of the selectivity filter. Our data indicate that in A463C potassium can bind within the selectivity filter without interfering with the process of C-type inactivation.

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15

Farag, N. E., D. Jeong, T. Claydon, J. Warwicker, and M. R. Boyett. "Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues." American Journal of Physiology-Cell Physiology 311, no. 2 (August 1, 2016): C255—C268. http://dx.doi.org/10.1152/ajpcell.00277.2015.

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Polyunsaturated fatty acids (PUFAs) modulate voltage-gated K+ channel inactivation by an unknown site and mechanism. The effects of ω-6 and ω-3 PUFAs were investigated on the heterologously expressed Kv1.4 channel. PUFAs inhibited wild-type Kv1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant Kv1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation ( Kd, 15–43 μM). C-type inactivation was affected by extracellular H+ and K+ as well as PUFAs and there was an interaction among the three: the effect of PUFAs was reversed during acidosis and abolished on raising K+. Replacement of two positively charged residues in the extracellular pore (H508 and K532) abolished the effects of the PUFAs (and extracellular H+ and K+) on C-type inactivation but had no effect on the lipoelectric modulation of voltage sensor activation, suggesting two separable interaction sites/mechanisms of action of PUFAs. Charge calculations suggest that the acidic head group of the PUFAs raises the pKa of H508 and this reduces the K+ occupancy of the selectivity filter, stabilizing the C-type inactivated state.

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16

Armstrong, Clay M., and Toshinori Hoshi. "K+ channel gating: C-type inactivation is enhanced by calcium or lanthanum outside." Journal of General Physiology 144, no. 3 (August 25, 2014): 221–30. http://dx.doi.org/10.1085/jgp.201411223.

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Many voltage-gated K+ channels exhibit C-type inactivation. This typically slow process has been hypothesized to result from dilation of the outer-most ring of the carbonyls in the selectivity filter, destroying this ring’s ability to bind K+ with high affinity. We report here strong enhancement of C-type inactivation upon extracellular addition of 10–40 mM Ca2+ or 5–50 µM La3+. These multivalent cations mildly increase the rate of C-type inactivation during depolarization and markedly promote inactivation and/or suppress recovery when membrane voltage (Vm) is at resting levels (−80 to −100 mV). At −80 mV with 40 mM Ca2+ and 0 mM K+ externally, ShBΔN channels with the mutation T449A inactivate almost completely within 2 min or less with no pulsing. This behavior is observed only in those mutants that show C-type inactivation on depolarization and is distinct from the effects of Ca2+ and La3+ on activation (opening and closing of the Vm-controlled gate), i.e., slower activation of K+ channels and a positive shift of the mid-voltage of activation. The Ca2+/La3+ effects on C-type inactivation are antagonized by extracellular K+ in the low millimolar range. This, together with the known ability of Ca2+ and La3+ to block inward current through K+ channels at negative voltage, strongly suggests that Ca2+/La3+ acts at the outer mouth of the selectivity filter. We propose that at −80 mV, Ca2+ or La3+ ions compete effectively with K+ at the channel’s outer mouth and prevent K+ from stabilizing the filter’s outer carbonyl ring.

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17

Kurata, Harley T., Gordon S. Soon, and David Fedida. "Altered State Dependence of C-Type Inactivation in the Long and Short Forms of Human Kv1.5." Journal of General Physiology 118, no. 3 (August 27, 2001): 315–32. http://dx.doi.org/10.1085/jgp.118.3.315.

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Evidence from both human and murine cardiomyocytes suggests that truncated isoforms of Kv1.5 can be expressed in vivo. Using whole-cell patch-clamp recordings, we have characterized the activation and inactivation properties of Kv1.5ΔN209, a naturally occurring short form of human Kv1.5 that lacks roughly 75% of the T1 domain. When expressed in HEK 293 cells, this truncated channel exhibited a V1/2 of −19.5 ± 0.9 mV for activation and −35.7 ± 0.7 mV for inactivation, compared with a V1/2 of −11.2 ± 0.3 mV for activation and −0.9 ± 1.6 mV for inactivation in full-length Kv.15. Kv1.5ΔN209 channels exhibited several features rarely observed in voltage-gated K+ channels and absent in full-length Kv1.5, including a U-shaped voltage dependence of inactivation and “excessive cumulative inactivation,” in which a train of repetitive depolarizations resulted in greater inactivation than a continuous pulse. Kv1.5ΔN209 also exhibited a stronger voltage dependence to recovery from inactivation, with the time to half-recovery changing e-fold over 30 mV compared with 66 mV in full-length Kv1.5. During trains of human action potential voltage clamps, Kv1.5ΔN209 showed 30–35% greater accumulated inactivation than full-length Kv1.5. These results can be explained with a model based on an allosteric model of inactivation in Kv2.1 (Klemic, K.G., C.-C. Shieh, G.E. Kirsch, and S.W. Jones. 1998. Biophys. J. 74:1779–1789) in which an absence of the NH2 terminus results in accelerated inactivation from closed states relative to full-length Kv1.5. We suggest that differential expression of isoforms of Kv1.5 may contribute to K+ current diversity in human heart and many other tissues.

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18

Basso, Claudia, Pedro Labarca, Enrico Stefani, Osvaldo Alvarez, and Ramon Latorre. "Pore accessibility during C-type inactivation in Shaker K+ channels." FEBS Letters 429, no. 3 (June 16, 1998): 375–80. http://dx.doi.org/10.1016/s0014-5793(98)00635-8.

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19

Ogielska, E. M., W. N. Zagotta, T. Hoshi, S. H. Heinemann, J. Haab, and R. W. Aldrich. "Cooperative subunit interactions in C-type inactivation of K channels." Biophysical Journal 69, no. 6 (December 1995): 2449–57. http://dx.doi.org/10.1016/s0006-3495(95)80114-1.

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20

Levy, D. I., and C. Deutsch. "Recovery from C-type inactivation is modulated by extracellular potassium." Biophysical Journal 70, no. 2 (February 1996): 798–805. http://dx.doi.org/10.1016/s0006-3495(96)79619-4.

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21

Jamieson, Quentin, and Stephen W. Jones. "Shaker IR T449 Mutants Separate C- from U-Type Inactivation." Journal of Membrane Biology 247, no. 4 (February 1, 2014): 319–30. http://dx.doi.org/10.1007/s00232-014-9634-3.

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22

Cordero-Morales, Julio F., Vishwanath Jogini, Sudha Chakrapani, and Eduardo Perozo. "A Multipoint Hydrogen-Bond Network Underlying KcsA C-Type Inactivation." Biophysical Journal 100, no. 10 (May 2011): 2387–93. http://dx.doi.org/10.1016/j.bpj.2011.01.073.

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23

Armstrong, Clay M., and Toshinori Hoshi. "Enhancement of C-Type Inactivation by External Ca2+ and La3+." Biophysical Journal 106, no. 2 (January 2014): 537a. http://dx.doi.org/10.1016/j.bpj.2013.11.2995.

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24

Lipinsky, Maya, William Sam Tobelaim, Asher Peretz, Luba Simhaev, Adva Yeheskel, Daniel Yakubovich, Guy Lebel, Yoav Paas, Joel A. Hirsch, and Bernard Attali. "A unique mechanism of inactivation gating of the Kv channel family member Kv7.1 and its modulation by PIP2 and calmodulin." Science Advances 6, no. 51 (December 2020): eabd6922. http://dx.doi.org/10.1126/sciadv.abd6922.

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Inactivation of voltage-gated K+ (Kv) channels mostly occurs by fast N-type or/and slow C-type mechanisms. Here, we characterized a unique mechanism of inactivation gating comprising two inactivation states in a member of the Kv channel superfamily, Kv7.1. Removal of external Ca2+ in wild-type Kv7.1 channels produced a large, voltage-dependent inactivation, which differed from N- or C-type mechanisms. Glu295 and Asp317 located, respectively, in the turret and pore entrance are involved in Ca2+ coordination, allowing Asp317 to form H-bonding with the pore helix Trp304, which stabilizes the selectivity filter and prevents inactivation. Phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+-calmodulin prevented Kv7.1 inactivation triggered by Ca2+-free external solutions, where Ser182 at the S2-S3 linker relays the calmodulin signal from its inner boundary to the external pore to allow proper channel conduction. Thus, we revealed a unique mechanism of inactivation gating in Kv7.1, exquisitely controlled by external Ca2+ and allosterically coupled by internal PIP2 and Ca2+-calmodulin.

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25

Nuanualsuwan, Suphachai, and Dean O. Cliver. "Infectivity of RNA from Inactivated Poliovirus." Applied and Environmental Microbiology 69, no. 3 (March 2003): 1629–32. http://dx.doi.org/10.1128/aem.69.3.1629-1632.2003.

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ABSTRACT During inactivation of poliovirus type 1 (PV-1) by exposure to UV, hypochlorite, and heat (72°C), the infectivity of the virus was compared with that of its RNA. DEAE-dextran (1-mg/ml concentration in Dulbecco's modified Eagle medium buffered with 0.05 M Tris, pH 7.4) was used to facilitate transfecting PV-1 RNA into FRhK-4 host cells. After interaction of PV-1 RNA with cell monolayer at room temperature (21 to 22°C) for 20 min, the monolayers were washed with 5 ml of Hanks balanced salt solution. The remainder of the procedure was the same as that for the conventional plaque technique, which was also used for quantifying the PV-1 whole-particle infectivity. Plaque formation by extracted RNA was approximately 100,000-fold less efficient than that by whole virions. The slopes of best-fit regression lines of inactivation curves for virion infectivity and RNA infectivity were compared to determine the target of inactivation. For UV and hypochlorite inactivation the slopes of inactivation curves of virion infectivity and RNA infectivity were not statistically different. However, the difference of slopes of inactivation curves of virion infectivity and RNA infectivity was statistically significant for thermal inactivation. The results of these experiments indicate that viral RNA is a primary target of UV and hypochlorite inactivations but that the sole target of thermal inactivation is the viral capsid.

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CALUGARU, Sergei V., Srinivasan KRISHNAN, Calvin J. CHANY, Barry G. HALL, and Michael L. SINNOTT. "Larger increases in sensitivity to paracatalytic inactivation than in catalytic competence during experimental evolution of the second β-galactosidase of Escherichia coli." Biochemical Journal 325, no. 1 (July 1, 1997): 117–21. http://dx.doi.org/10.1042/bj3250117.

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Second-order rate constants (M-1·s-1) at 25 °C and pH 7.5 for inactivation of first-generation (ebga and ebgb), second-generation(ebgab and ebgabcd) and third-generation (ebgabcde) experimental evolvants of the title enzyme by 2′,4′-dinitrophenyl 2-deoxy-2-fluoro-β-d-galactopyranoside are 0.042, 0.30, 10, 24 and 57 respectively. Only partial inactivation is observed, except forebgabcde. At a single high inactivator concentration, inactivation of the wild-type ebgo is also seen. The changes in sensitivity to the paracatalytic inactivator (over a range of 103.3) are larger than changes in kcat/Km for lactose (over a range of 102.7) or nitrophenyl galactosides (over a range of only 101.3), or changes in degalactosylation rate (over a range of 101.7). These data raise the possibility that evolution in the reverse sense, towards insensitivity to a paracatalytic inactivator with a proportionally lower effect on transformation of substrate, may become a mechanism for the development of bacterial resistance to antibiotics that act by paracatalytic enzyme inactivation.

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27

Decrey, Loïc, Shinobu Kazama, and Tamar Kohn. "Ammonia as anIn SituSanitizer: Influence of Virus Genome Type on Inactivation." Applied and Environmental Microbiology 82, no. 16 (June 3, 2016): 4909–20. http://dx.doi.org/10.1128/aem.01106-16.

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ABSTRACTTreatment of human excreta and animal manure (HEAM) is key in controlling the spread of persistent enteric pathogens, such as viruses. The extent of virus inactivation during HEAM storage and treatment appears to vary with virus genome type, although the reasons for this variability are not clear. Here, we investigated the inactivation of viruses of different genome types under conditions representative of HEAM storage or mesophilic digestion. The goals were to characterize the influence of HEAM solution conditions on inactivation and to determine the potential mechanisms involved. Specifically, eight viruses representing the four viral genome types (single-stranded RNA [ssRNA], double-stranded RNA [dsRNA], single-stranded DNA [ssDNA], and double-stranded DNA [dsDNA]) were exposed to synthetic solutions with well-controlled temperature (20 to 35°C), pH (8 to 9), and ammonia (NH3) concentrations (0 to 40 mmol liter−1). DNA and dsRNA viruses were considerably more resistant than ssRNA viruses, resulting in up to 1,000-fold-longer treatment times to reach a 4-log inactivation. The apparently slower inactivation of DNA viruses was rationalized by the higher stability of DNA than that of ssRNA in HEAM. Pushing the system toward harsher pH (>9) and temperature (>35°C) conditions, such as those encountered in thermophilic digestion and alkaline treatments, led to more consistent inactivation kinetics among ssRNA and other viruses. This suggests that the dependence of inactivation on genome type disappeared in favor of protein-mediated inactivation mechanisms common to all viruses. Finally, we recommend the use of MS2 as a conservative indicator to assess the inactivation of ssRNA viruses and the stable ΦX174 or dsDNA phages as indicators for persistent viruses.IMPORTANCEViruses are among the most environmentally persistent pathogens. They can be present in high concentrations in human excreta and animal manure (HEAM). Therefore, appropriate treatment of HEAM is important prior to its reuse or discharge into the environment. Here, we investigated the factors that determine the persistence of viruses in HEAM, and we determined the main mechanisms that lead to their inactivation. Unlike other organisms, viruses can have four different genome types (double- or single-stranded RNA or DNA), and the viruses studied herein represent all four types. Genome type appeared to be the major determinant for persistence. Single-stranded RNA viruses are the most labile, because this genome type is susceptible to degradation in HEAM. In contrast, the other genome types are more stable; therefore, inactivation is slower and mainly driven by the degradation of viral proteins. Overall, this study allows us to better understand the behavior of viruses in HEAM.

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González-Pérez, Vivian, Alan Neely, Christian Tapia, Giovanni González-Gutiérrez, Gustavo Contreras, Patricio Orio, Verónica Lagos, et al. "Slow Inactivation in Shaker K Channels Is Delayed by Intracellular Tetraethylammonium." Journal of General Physiology 132, no. 6 (November 24, 2008): 633–50. http://dx.doi.org/10.1085/jgp.200810057.

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After removal of the fast N-type inactivation gate, voltage-sensitive Shaker (Shaker IR) K channels are still able to inactivate, albeit slowly, upon sustained depolarization. The classical mechanism proposed for the slow inactivation observed in cell-free membrane patches—the so called C inactivation—is a constriction of the external mouth of the channel pore that prevents K+ ion conduction. This constriction is antagonized by the external application of the pore blocker tetraethylammonium (TEA). In contrast to C inactivation, here we show that, when recorded in whole Xenopus oocytes, slow inactivation kinetics in Shaker IR K channels is poorly dependent on external TEA but severely delayed by internal TEA. Based on the antagonism with internally or externally added TEA, we used a two-pulse protocol to show that half of the channels inactivate by way of a gate sensitive to internal TEA. Such gate had a recovery time course in the tens of milliseconds range when the interpulse voltage was −90 mV, whereas C-inactivated channels took several seconds to recover. Internal TEA also reduced gating charge conversion associated to slow inactivation, suggesting that the closing of the internal TEA-sensitive inactivation gate could be associated with a significant amount of charge exchange of this type. We interpreted our data assuming that binding of internal TEA antagonized with U-type inactivation (Klemic, K.G., G.E. Kirsch, and S.W. Jones. 2001. Biophys. J. 81:814–826). Our results are consistent with a direct steric interference of internal TEA with an internally located slow inactivation gate as a “foot in the door” mechanism, implying a significant functional overlap between the gate of the internal TEA-sensitive slow inactivation and the primary activation gate. But, because U-type inactivation is reduced by channel opening, trapping the channel in the open conformation by TEA would also yield to an allosteric delay of slow inactivation. These results provide a framework to explain why constitutively C-inactivated channels exhibit gating charge conversion, and why mutations at the internal exit of the pore, such as those associated to episodic ataxia type I in hKv1.1, cause severe changes in inactivation kinetics.

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Wang, Jinling, Matthew C. Trudeau, Angelina M. Zappia, and Gail A. Robertson. "Regulation of Deactivation by an Amino Terminal Domain in Human Ether-à-go-go –related Gene Potassium Channels." Journal of General Physiology 112, no. 5 (November 1, 1998): 637–47. http://dx.doi.org/10.1085/jgp.112.5.637.

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Abnormalities in repolarization of the cardiac ventricular action potential can lead to life-threatening arrhythmias associated with long QT syndrome. The repolarization process depends upon the gating properties of potassium channels encoded by the human ether-à-go-go–related gene (HERG), especially those governing the rate of recovery from inactivation and the rate of deactivation. Previous studies have demonstrated that deletion of the NH2 terminus increases the deactivation rate, but the mechanism by which the NH2 terminus regulates deactivation in wild-type channels has not been elucidated. We tested the hypothesis that the HERG NH2 terminus slows deactivation by a mechanism similar to N-type inactivation in Shaker channels, where it binds to the internal mouth of the pore and prevents channel closure. We found that the regulation of deactivation by the HERG NH2 terminus bears similarity to Shaker N-type inactivation in three respects: (a) deletion of the NH2 terminus slows C-type inactivation; (b) the action of the NH2 terminus is sensitive to elevated concentrations of external K+, as if its binding along the permeation pathway is disrupted by K+ influx; and (c) N-ethylmaleimide, covalently linked to an aphenotypic cysteine introduced within the S4–S5 linker, mimics the N deletion phenotype, as if the binding of the NH2 terminus to its receptor site were hindered. In contrast to N-type inactivation in Shaker, however, there was no indication that the NH2 terminus blocks the HERG pore. In addition, we discovered that separate domains within the NH2 terminus mediate the slowing of deactivation and the promotion of C-type inactivation. These results suggest that the NH2 terminus stabilizes the open state and, by a separate mechanism, promotes C-type inactivation.

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Li, Jing, Jared Ostmeyer, Luis G. Cuello, Eduardo Perozo, and Benoît Roux. "Rapid constriction of the selectivity filter underlies C-type inactivation in the KcsA potassium channel." Journal of General Physiology 150, no. 10 (August 2, 2018): 1408–20. http://dx.doi.org/10.1085/jgp.201812082.

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C-type inactivation is a time-dependent process observed in many K+ channels whereby prolonged activation by an external stimulus leads to a reduction in ionic conduction. While C-type inactivation is thought to be a result of a constriction of the selectivity filter, the local dynamics of the process remain elusive. Here, we use molecular dynamics (MD) simulations of the KcsA channel to elucidate the nature of kinetically delayed activation/inactivation gating coupling. Microsecond-scale MD simulations based on the truncated form of the KcsA channel (C-terminal domain deleted) provide a first glimpse of the onset of C-type inactivation. We observe over multiple trajectories that the selectivity filter consistently undergoes a spontaneous and rapid (within 1–2 µs) transition to a constricted conformation when the intracellular activation gate is fully open, but remains in the conductive conformation when the activation gate is closed or partially open. Multidimensional umbrella sampling potential of mean force calculations and nonequilibrium voltage-driven simulations further confirm these observations. Electrophysiological measurements show that the truncated form of the KcsA channel inactivates faster and greater than full-length KcsA, which is consistent with truncated KcsA opening to a greater degree because of the absence of the C-terminal domain restraint. Together, these results imply that the observed kinetics underlying activation/inactivation gating reflect a rapid conductive-to-constricted transition of the selectivity filter that is allosterically controlled by the slow opening of the intracellular gate.

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Shirokov, Roman, Gonzalo Ferreira, Jianxun Yi, and Eduardo Ríos. "Inactivation of Gating Currents of L-Type Calcium Channels." Journal of General Physiology 111, no. 6 (June 1, 1998): 807–23. http://dx.doi.org/10.1085/jgp.111.6.807.

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In studies of gating currents of rabbit cardiac Ca channels expressed as α1C/β2a or α1C/β2a/α2δ subunit combinations in tsA201 cells, we found that long-lasting depolarization shifted the distribution of mobile charge to very negative potentials. The phenomenon has been termed charge interconversion in native skeletal muscle (Brum, G., and E. Ríos. 1987. J. Physiol. (Camb.). 387:489–517) and cardiac Ca channels (Shirokov, R., R. Levis, N. Shirokova, and E. Ríos. 1992. J. Gen. Physiol. 99:863–895). Charge 1 (voltage of half-maximal transfer, V1/2 ≃ 0 mV) gates noninactivated channels, while charge 2 (V1/2 ≃ −90 mV) is generated in inactivated channels. In α1C/β2a cells, the available charge 1 decreased upon inactivating depolarization with a time constant τ ≃ 8, while the available charge 2 decreased upon recovery from inactivation (at −200 mV) with τ ≃ 0.3 s. These processes therefore are much slower than charge movement, which takes <50 ms. This separation between the time scale of measurable charge movement and that of changes in their availability, which was even wider in the presence of α2δ, implies that charges 1 and 2 originate from separate channel modes. Because clear modal separation characterizes slow (C-type) inactivation of Na and K channels, this observation establishes the nature of voltage-dependent inactivation of L-type Ca channels as slow or C-type. The presence of the α2δ subunit did not change the V1/2 of charge 2, but sped up the reduction of charge 1 upon inactivation at 40 mV (to τ ≃ 2 s), while slowing the reduction of charge 2 upon recovery (τ ≃ 2 s). The observations were well simulated with a model that describes activation as continuous electrodiffusion (Levitt, D. 1989. Biophys. J. 55:489–498) and inactivation as discrete modal change. The effects of α2δ are reproduced assuming that the subunit lowers the free energy of the inactivated mode.

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Zhang, Shetuan, Harley T. Kurata, Steven J. Kehl, and David Fedida. "Rapid Induction of P/C-type Inactivation Is the Mechanism for Acid-induced K+ Current Inhibition." Journal of General Physiology 121, no. 3 (February 24, 2003): 215–25. http://dx.doi.org/10.1085/jgp.20028760.

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Extracellular acidification is known to decrease the conductance of many voltage-gated potassium channels. In the present study, we investigated the mechanism of H+o-induced current inhibition by taking advantage of Na+ permeation through inactivated channels. In hKv1.5, H+o inhibited open-state Na+ current with a similar potency to K+ current, but had little effect on the amplitude of inactivated-state Na+ current. In support of inactivation as the mechanism for the current reduction, Na+ current through noninactivating hKv1.5-R487V channels was not affected by [H+o]. At pH 6.4, channels were maximally inactivated as soon as sufficient time was given to allow activation, which suggested two possibilities for the mechanism of action of H+o. These were that inactivation of channels in early closed states occurred while hyperpolarized during exposure to acid pH (closed-state inactivation) and/or inactivation from the open state was greatly accelerated at low pH. The absence of outward Na+ currents but the maintained presence of slow Na+ tail currents, combined with changes in the Na+ tail current time course at pH 6.4, led us to favor the hypothesis that a reduction in the activation energy for the inactivation transition from the open state underlies the inhibition of hKv1.5 Na+ current at low pH.

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CREST, M., E. EHILE, T. PIN, K. WATANABE, and M. GOLA. "Plateau-Generating Nerve Cells in Helix: Properties of the Repolarizing Voltage-Gated and Ca2+-Activated Potassium Currents." Journal of Experimental Biology 152, no. 1 (September 1, 1990): 211–41. http://dx.doi.org/10.1242/jeb.152.1.211.

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The aim of this study was to identify and characterize the repolarizing currents present in Helix nerve cells that generate long-lasting Ca2+-dependent depolarized plateaus in response to low-frequency stimulation. Two K+ currents were identified: a voltage-gated K(V) current and a Ca2+-activated K+ current or C current. These currents were studied separately in cells injected with either EGTA, tetraethylammonium (TEA+) or Cs+. C current activation was found to be rate-limited by the size of the inward Ca2+ current. Both K(V) and C currents displayed a pronounced relaxation during sustained depolarizations. Inactivation of the K(V) current was voltage-dependent. Inactivation of the C current was induced by either tiny Ca2+ entries or intracellular Ca2+ injections; C current inactivation was found to be more sensitive to intracellular [Ca2+] than the activating process. Similar experiments performed on various nerve cells revealed that the amount and rate of inactivation of both currents, but not their gating properties, varied greatly from cell to cell; plateau-generating cells had the strongest inactivating processes acting on both K+ currents. These properties help to explain how regular firing may turn into long-lasting depolarized plateaus. They point to the existence of cellular processes that might regulate the number of available K+ channels in a manner that is specific to the nerve cell type. Note: To whom reprint requests should be addressed.

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Panaghie, Gianina, Kerry Purtell, Kwok-Keung Tai, and Geoffrey W. Abbott. "Voltage-Dependent C-Type Inactivation in a Constitutively Open K+ Channel." Biophysical Journal 95, no. 6 (September 2008): 2759–78. http://dx.doi.org/10.1529/biophysj.108.133678.

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Ghadikolaei, Azadeh Nikouee, and Stephan Grissmer. "Scorpion Toxins Modify C-Type Inactivation in a Mutant Potassium Channel." Biophysical Journal 100, no. 3 (February 2011): 566a. http://dx.doi.org/10.1016/j.bpj.2010.12.3285.

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Pérez-Cornejo, Patricia. "H + ion modulation of C-type inactivation of Shaker K + channels." Pfl�gers Archiv European Journal of Physiology 437, no. 6 (April 22, 1999): 865–70. http://dx.doi.org/10.1007/s004240050856.

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Li, Jing, Jared Jostmey, Eduardo Perozo, and Benoit Roux. "A Universal Molecular Mechanism for C-type Inactivation in Potassium Channels." Biophysical Journal 114, no. 3 (February 2018): 474a—475a. http://dx.doi.org/10.1016/j.bpj.2017.11.2611.

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Chen, Yi-Hung, King-Chuen Wu, Chin-Tsang Yang, Yuan-Kun Tu, Chi-Li Gong, Chia-Chia Chao, Min-Fan Tsai, Yue-Hsiung Kuo, and Yuk-Man Leung. "Coumarsabin hastens C-type inactivation gating of voltage-gated K+ channels." European Journal of Pharmacology 704, no. 1-3 (March 2013): 41–48. http://dx.doi.org/10.1016/j.ejphar.2013.01.062.

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Conti, Luca, Jakob Renhorn, Anders Gabrielsson, Fredrik Turesson, Sara Liin, Erik Lindahl, and Fredrik Elinder. "A Reciprocal Voltage Sensor-To-Pore Coupling in C-Type Inactivation." Biophysical Journal 110, no. 3 (February 2016): 104a. http://dx.doi.org/10.1016/j.bpj.2015.11.620.

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YELLEN, GARY. "The moving parts of voltage-gated ion channels." Quarterly Reviews of Biophysics 31, no. 3 (August 1998): 239–95. http://dx.doi.org/10.1017/s0033583598003448.

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Ion channels, like many other proteins, have moving parts that perform useful functions. The channel proteins contain an aqueous, ion-selective pore that crosses the plasma membrane, and they use a number of distinct ‘gating’ mechanisms to open and close this pore in response to biological stimuli such as the binding of a ligand or a change in the transmembrane voltage.This review is written at a watershed in our understanding of ion channels.1. INTRODUCTION 2401.1 Basic structure of voltage-activated channels 2411.2 What are the physical motions of the channel protein during gating? 2431.3 Gating involves several distinct mechanisms of activation and inactivation 2462. ACTIVATION GATING 2462.1 Early evidence for an activation gate at the intracellular mouth 2472.1.1 Open channel blockade 2472.1.2 The ‘ foot-in-the-door’ effect 2492.1.3 Trapping of blockers behind closed activation gates 2492.2 Site-directed mutagenesis and the difficulty of inferring structural roles from functional effects 2502.3 State-dependent cysteine modification as a reporter of position and motion 2512.4 Localization of activation gating 2542.4.1 The trapping cavity 2542.4.2 The activation gate 2552.4.3 Is there more than one site of activation gating? 2583. INACTIVATION GATING 2593.1 Ball-and-chain (N-type) inactivation 2613.1.1 Nature of the ‘ball’ – a tethered blocking particle 2623.1.2 The ball receptor 2633.1.3 The chain 2643.1.4 Variations on the N-type inactivation theme: multiple balls, foreign balls, anti-balls 2653.2 C-type inactivation 2663.2.1 C-type inactivation and the outer mouth of the K+channel 2663.2.2 The selectivity filter participates in C-type inactivation 2673.2.3 A consistent structural picture of C-type inactivation 2693.3 By what mechanism do other voltage-gated channels inactivate? 2724. THE VOLTAGE SENSOR 2734.1 Quantitative principles of voltage-dependent gating 2764.2 S4 (and its neighbours) as the principal voltage sensor 2774.2.1 Mutational effects on voltage-dependence and charge movement 2774.2.2 Evidence for the translocation of S4 2794.2.3 Real-time monitoring of S4motion by fluorescence 2824.3 Coupling between the voltage sensor and gating 2835. CONCLUSION 2846. ACKNOWLEDGEMENTS 2877. REFERENCES 287

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Starkus, John G., Lioba Kuschel, Martin D. Rayner, and Stefan H. Heinemann. "Macroscopic Na+ Currents in the “Nonconducting” Shaker Potassium Channel Mutant W434F." Journal of General Physiology 112, no. 1 (July 1, 1998): 85–93. http://dx.doi.org/10.1085/jgp.112.1.85.

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C-type inactivation in Shaker potassium channels inhibits K+ permeation. The associated structural changes appear to involve the outer region of the pore. Recently, we have shown that C-type inactivation involves a change in the selectivity of the Shaker channel, such that C-type inactivated channels show maintained voltage-sensitive activation and deactivation of Na+ and Li+ currents in K+-free solutions, although they show no measurable ionic currents in physiological solutions. In addition, it appears that the effective block of ion conduction produced by the mutation W434F in the pore region may be associated with permanent C-type inactivation of W434F channels. These conclusions predict that permanently C-type inactivated W434F channels would also show Na+ and Li+ currents (in K+-free solutions) with kinetics similar to those seen in C-type-inactivated Shaker channels. This paper confirms that prediction and demonstrates that activation and deactivation parameters for this mutant can be obtained from macroscopic ionic current measurements. We also show that the prolonged Na+ tail currents typical of C-type inactivated channels involve an equivalent prolongation of the return of gating charge, thus demonstrating that the kinetics of gating charge return in W434F channels can be markedly altered by changes in ionic conditions.

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Gomez-Lagunas, Froylan, Imilla Arias-Olguin, and Elisa Carrillo. "Shab K Channel Slow Inactivation. A Mechanism that Departs from Both C and U-Type Inactivation Mechanisms." Biophysical Journal 102, no. 3 (January 2012): 530a. http://dx.doi.org/10.1016/j.bpj.2011.11.2896.

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Takagi, Shuichi, Yasuki Kihara, Shigetake Sasayama, and Tamotsu Mitsuiye. "Slow inactivation of cardiac L-type Ca2+ channel induced by cold acclimation of guinea pig." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274, no. 2 (February 1, 1998): R348—R356. http://dx.doi.org/10.1152/ajpregu.1998.274.2.r348.

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Whole cell L-type Ca2+ current was recorded in ventricular myocytes dissociated from guinea pigs that were bred at ambient temperatures ranging between daily averages of 4 and 29°C. The dynamic voltage range of inactivation, as measured using 400-ms conditioning pulses and a holding potential of −40 mV, extended from −50 to −20 mV in myocytes prepared in summer. In winter, the inactivation curve was shifted to more negative potentials than in summer. Double-pulse experiments revealed that the negative shift was due to slow-inactivation kinetics. The negative shift of inactivation could be induced in myocytes prepared from animals that had been kept at 5°C for >3 wk in the summer. The negative shift in Ca2+ current inactivation could be abolished by adding guanosine 5′- O-(2-thiodiphosphate) (5 mM) to the pipette solution, but not by adding staurosporine (2 μM) or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (100 μM) to the bath. The cold acclimation may introduce the slow inactivation of the cardiac L-type Ca2+ channel through an unknown pertussis toxin-insensitive G protein.

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Rasmusson, R. L., M. J. Morales, R. C. Castellino, Y. Zhang, D. L. Campbell, and H. C. Strauss. "C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes." Journal of Physiology 489, no. 3 (December 15, 1995): 709–21. http://dx.doi.org/10.1113/jphysiol.1995.sp021085.

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Garg, Vivek, Frank B. Sachse, and Michael C. Sanguinetti. "Tuning of EAG K+ channel inactivation: Molecular determinants of amplification by mutations and a small molecule." Journal of General Physiology 140, no. 3 (August 27, 2012): 307–24. http://dx.doi.org/10.1085/jgp.201210826.

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Ether-à-go-go (EAG) and EAG-related gene (ERG) K+ channels are close homologues but differ markedly in their gating properties. ERG1 channels are characterized by rapid and extensive C-type inactivation, whereas mammalian EAG1 channels were previously considered noninactivating. Here, we show that human EAG1 channels exhibit an intrinsic voltage-dependent slow inactivation that is markedly enhanced in rate and extent by 1–10 µM 3-nitro-N-(4-phenoxyphenyl) benzamide, or ICA105574 (ICA). This compound was previously reported to have the opposite effect on ERG1 channels, causing an increase in current magnitude by inhibition of C-type inactivation. The voltage dependence of 2 µM ICA-induced inhibition of EAG1 current was half-maximal at −73 mV, 62 mV negative to the half-point for channel activation. This finding suggests that current inhibition by the drug is mediated by enhanced inactivation and not open-channel block, where the voltage half-points for current inhibition and channel activation are predicted to overlap, as we demonstrate for clofilium and astemizole. The mutation Y464A in the S6 segment also induced inactivation of EAG1, with a time course and voltage dependence similar to that caused by 2 µM ICA. Several Markov models were investigated to describe gating effects induced by multiple concentrations of the drug and the Y464A mutation. Models with the smallest fit error required both closed- and open-state inactivation. Unlike typical C-type inactivation, the rate of Y464A- and ICA-induced inactivation was not decreased by external tetraethylammonium or elevated [K+]e. EAG1 channel inactivation introduced by Y464A was prevented by additional mutation of a nearby residue located in the S5 segment (F359A) or pore helix (L434A), suggesting a tripartite molecular model where interactions between single residues in S5, S6, and the pore helix modulate inactivation of EAG1 channels.

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Bett, Glenna C. L., Isidore Dinga-Madou, Qinlian Zhou, Vladimir E. Bondarenko, and Randall L. Rasmusson. "A Model of the Interaction between N-type and C-type Inactivation in Kv1.4 Channels." Biophysical Journal 100, no. 1 (January 2011): 11–21. http://dx.doi.org/10.1016/j.bpj.2010.11.011.

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Wu, Wei, Alison Gardner, and Michael C. Sanguinetti. "Cooperative subunit interactions mediate fast C-type inactivation of hERG1 K+channels." Journal of Physiology 592, no. 20 (September 3, 2014): 4465–80. http://dx.doi.org/10.1113/jphysiol.2014.277483.

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Levy, D. I., and C. Deutsch. "A voltage-dependent role for K+ in recovery from C-type inactivation." Biophysical Journal 71, no. 6 (December 1996): 3157–66. http://dx.doi.org/10.1016/s0006-3495(96)79509-7.

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Hoshi, Toshinori, and Clay M. Armstrong. "C-type inactivation of voltage-gated K+ channels: Pore constriction or dilation?" Journal of General Physiology 141, no. 2 (January 14, 2013): 151–60. http://dx.doi.org/10.1085/jgp.201210888.

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Kunikova, E. D., N. V. Moroz, M. A. Dolgova, L. V. Malakhova, and I. A. Komarov. "Optimization of RHDV type 1 and 2 inactivation modes." Veterinary Science Today 1, no. 1 (March 29, 2021): 22–28. http://dx.doi.org/10.29326/2304-196x-2021-1-36-22-28.

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The purpose of these studies was to optimize RHDV type 1 and 2 (RHDV1 and RHDV2) inactivation modes to use the obtained antigens in inactivated vaccines and diagnosticums. The inactivating effect of aminoethylethylenimine and β-propiolactone was studied in different concentrations in correlation with the exposure time and temperature. The correlation between the inactivating effect of the compound used and the accepted test conditions (concentration, temperature, and exposure time) was studied on a group of rabbits, each of which was injected intramuscularly with 1 cm3 of the inactivated material sample. At the end of the maximum exposure interval, a control sample of the viral material, kept under the same conditions without any inactivant added was similarly tested. Lethality was considered to evaluate the damaging action in the test and control groups: L = m/n, where m is the number of dead animals; n is the total number of rabbits in the group for testing of the inactivated material sample. The postmortem diagnosis was confirmed by testing the rabbit liver tissue homogenate for relative antigens using ELISA. It was found that aminoethylethylenimine and β-propiolactone did not have the same effect on the studied variants of the virus. In order to preserve at maximum the antigenic structures of the virus, the following inactivation modes were considered to be optimal: for RHDV1-aminoethylethylenimine at a concentration of 0.3% at 37 °C, exposure time – 72 hours, or β-propiolactone at a concentration of 0.1–0.3% at 25–37 °С, exposure time – 24–48 hours; for RHDV2 – aminoethylethylenimine at a concentration of 1% at 37 °C, exposure time – 72 hours, or β-propiolactone at a concentration 0.3% at 25 °С, exposure time – 24 hours.

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Journal articles on the topic 'C-type inactivation'

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