Abstract
We previously concluded that the Kv2.1 K(+) channel inactivates preferentially from partially activated closed states. We report here that the Kv3.1 channel also exhibits two key features of this inactivation mechanism: a U-shaped voltage dependence measured at 10 s and stronger inactivation with repetitive pulses than with a single long depolarization. More surprisingly, slow inactivation of the Kv1 Shaker K(+) channel (Shaker B Delta 6--46) also has a U-shaped voltage dependence for 10-s depolarizations. The time and voltage dependence of recovery from inactivation reveals two distinct components for Shaker. Strong depolarizations favor inactivation that is reduced by K(o)(+) or by partial block by TEA(o), as previously reported for slow inactivation of Shaker. However, depolarizations near 0 mV favor inactivation that recovers rapidly, with strong voltage dependence (as for Kv2.1 and 3.1). The fraction of channels that recover rapidly is increased in TEA(o) or high K(o)(+). We introduce the term U-type inactivation for the mechanism that is dominant in Kv2.1 and Kv3.1. U-type inactivation also makes a major but previously unrecognized contribution to slow inactivation of Shaker.
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Selected References
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- Baukrowitz T., Yellen G. Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms. Neuron. 1995 Oct;15(4):951–960. doi: 10.1016/0896-6273(95)90185-x. [DOI] [PubMed] [Google Scholar]
 - Baukrowitz T., Yellen G. Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel. Science. 1996 Feb 2;271(5249):653–656. doi: 10.1126/science.271.5249.653. [DOI] [PubMed] [Google Scholar]
 - Bezanilla F., Perozo E., Stefani E. Gating of Shaker K+ channels: II. The components of gating currents and a model of channel activation. Biophys J. 1994 Apr;66(4):1011–1021. doi: 10.1016/S0006-3495(94)80882-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Cahalan M. D., Chandy K. G., DeCoursey T. E., Gupta S. A voltage-gated potassium channel in human T lymphocytes. J Physiol. 1985 Jan;358:197–237. doi: 10.1113/jphysiol.1985.sp015548. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Chen J., Avdonin V., Ciorba M. A., Heinemann S. H., Hoshi T. Acceleration of P/C-type inactivation in voltage-gated K(+) channels by methionine oxidation. Biophys J. 2000 Jan;78(1):174–187. doi: 10.1016/S0006-3495(00)76583-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Choi K. L., Aldrich R. W., Yellen G. Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5092–5095. doi: 10.1073/pnas.88.12.5092. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - De Biasi M., Hartmann H. A., Drewe J. A., Taglialatela M., Brown A. M., Kirsch G. E. Inactivation determined by a single site in K+ pores. Pflugers Arch. 1993 Jan;422(4):354–363. doi: 10.1007/BF00374291. [DOI] [PubMed] [Google Scholar]
 - Erisir A., Lau D., Rudy B., Leonard C. S. Function of specific K(+) channels in sustained high-frequency firing of fast-spiking neocortical interneurons. J Neurophysiol. 1999 Nov;82(5):2476–2489. doi: 10.1152/jn.1999.82.5.2476. [DOI] [PubMed] [Google Scholar]
 - Grissmer S., Cahalan M. TEA prevents inactivation while blocking open K+ channels in human T lymphocytes. Biophys J. 1989 Jan;55(1):203–206. doi: 10.1016/S0006-3495(89)82793-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Hoshi T., Zagotta W. N., Aldrich R. W. Biophysical and molecular mechanisms of Shaker potassium channel inactivation. Science. 1990 Oct 26;250(4980):533–538. doi: 10.1126/science.2122519. [DOI] [PubMed] [Google Scholar]
 - Hoshi T., Zagotta W. N., Aldrich R. W. Shaker potassium channel gating. I: Transitions near the open state. J Gen Physiol. 1994 Feb;103(2):249–278. doi: 10.1085/jgp.103.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Hoshi T., Zagotta W. N., Aldrich R. W. Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region. Neuron. 1991 Oct;7(4):547–556. doi: 10.1016/0896-6273(91)90367-9. [DOI] [PubMed] [Google Scholar]
 - Immke D., Wood M., Kiss L., Korn S. J. Potassium-dependent changes in the conformation of the Kv2.1 potassium channel pore. J Gen Physiol. 1999 Jun;113(6):819–836. doi: 10.1085/jgp.113.6.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Jerng H. H., Covarrubias M. K+ channel inactivation mediated by the concerted action of the cytoplasmic N- and C-terminal domains. Biophys J. 1997 Jan;72(1):163–174. doi: 10.1016/S0006-3495(97)78655-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Jerng H. H., Shahidullah M., Covarrubias M. Inactivation gating of Kv4 potassium channels: molecular interactions involving the inner vestibule of the pore. J Gen Physiol. 1999 May;113(5):641–660. doi: 10.1085/jgp.113.5.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Kerschensteiner D., Stocker M. Heteromeric assembly of Kv2.1 with Kv9.3: effect on the state dependence of inactivation. Biophys J. 1999 Jul;77(1):248–257. doi: 10.1016/S0006-3495(99)76886-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Kiss L., Korn S. J. Modulation of C-type inactivation by K+ at the potassium channel selectivity filter. Biophys J. 1998 Apr;74(4):1840–1849. doi: 10.1016/S0006-3495(98)77894-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Klemic K. G., Shieh C. C., Kirsch G. E., Jones S. W. Inactivation of Kv2.1 potassium channels. Biophys J. 1998 Apr;74(4):1779–1789. doi: 10.1016/S0006-3495(98)77888-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Kramer J. W., Post M. A., Brown A. M., Kirsch G. E. Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits. Am J Physiol. 1998 Jun;274(6 Pt 1):C1501–C1510. doi: 10.1152/ajpcell.1998.274.6.C1501. [DOI] [PubMed] [Google Scholar]
 - Kuo C. C., Bean B. P. Na+ channels must deactivate to recover from inactivation. Neuron. 1994 Apr;12(4):819–829. doi: 10.1016/0896-6273(94)90335-2. [DOI] [PubMed] [Google Scholar]
 - Levy D. I., Deutsch C. A voltage-dependent role for K+ in recovery from C-type inactivation. Biophys J. 1996 Dec;71(6):3157–3166. doi: 10.1016/S0006-3495(96)79509-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Levy D. I., Deutsch C. Recovery from C-type inactivation is modulated by extracellular potassium. Biophys J. 1996 Feb;70(2):798–805. doi: 10.1016/S0006-3495(96)79619-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Liu Y., Jurman M. E., Yellen G. Dynamic rearrangement of the outer mouth of a K+ channel during gating. Neuron. 1996 Apr;16(4):859–867. doi: 10.1016/s0896-6273(00)80106-3. [DOI] [PubMed] [Google Scholar]
 - Loots E., Isacoff E. Y. Protein rearrangements underlying slow inactivation of the Shaker K+ channel. J Gen Physiol. 1998 Oct;112(4):377–389. doi: 10.1085/jgp.112.4.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - López-Barneo J., Hoshi T., Heinemann S. H., Aldrich R. W. Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels. Receptors Channels. 1993;1(1):61–71. [PubMed] [Google Scholar]
 - Marom S., Goldstein S. A., Kupper J., Levitan I. B. Mechanism and modulation of inactivation of the Kv3 potassium channel. Receptors Channels. 1993;1(1):81–88. [PubMed] [Google Scholar]
 - Meyer R., Heinemann S. H. Temperature and pressure dependence of Shaker K+ channel N- and C-type inactivation. Eur Biophys J. 1997;26(6):433–445. doi: 10.1007/s002490050098. [DOI] [PubMed] [Google Scholar]
 - Molina A., Castellano A. G., López-Barneo J. Pore mutations in Shaker K+ channels distinguish between the sites of tetraethylammonium blockade and C-type inactivation. J Physiol. 1997 Mar 1;499(Pt 2):361–367. doi: 10.1113/jphysiol.1997.sp021933. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Olcese R., Latorre R., Toro L., Bezanilla F., Stefani E. Correlation between charge movement and ionic current during slow inactivation in Shaker K+ channels. J Gen Physiol. 1997 Nov;110(5):579–589. doi: 10.1085/jgp.110.5.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Patil P. G., Brody D. L., Yue D. T. Preferential closed-state inactivation of neuronal calcium channels. Neuron. 1998 May;20(5):1027–1038. doi: 10.1016/s0896-6273(00)80483-3. [DOI] [PubMed] [Google Scholar]
 - Rasmusson R. L., Morales M. J., Castellino R. C., Zhang Y., Campbell D. L., Strauss H. C. C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes. J Physiol. 1995 Dec 15;489(Pt 3):709–721. doi: 10.1113/jphysiol.1995.sp021085. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Rettig J., Wunder F., Stocker M., Lichtinghagen R., Mastiaux F., Beckh S., Kues W., Pedarzani P., Schröter K. H., Ruppersberg J. P. Characterization of a Shaw-related potassium channel family in rat brain. EMBO J. 1992 Jul;11(7):2473–2486. doi: 10.1002/j.1460-2075.1992.tb05312.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Rich T. C., Snyders D. J. Evidence for multiple open and inactivated states of the hKv1.5 delayed rectifier. Biophys J. 1998 Jul;75(1):183–195. doi: 10.1016/S0006-3495(98)77505-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Schreibmayer W., Lester H. A., Dascal N. Voltage clamping of Xenopus laevis oocytes utilizing agarose-cushion electrodes. Pflugers Arch. 1994 Mar;426(5):453–458. doi: 10.1007/BF00388310. [DOI] [PubMed] [Google Scholar]
 - Schönherr R., Heinemann S. H. Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel. J Physiol. 1996 Jun 15;493(Pt 3):635–642. doi: 10.1113/jphysiol.1996.sp021410. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Serrano J. R., Perez-Reyes E., Jones S. W. State-dependent inactivation of the alpha1G T-type calcium channel. J Gen Physiol. 1999 Aug;114(2):185–201. doi: 10.1085/jgp.114.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Shieh C. C., Klemic K. G., Kirsch G. E. Role of transmembrane segment S5 on gating of voltage-dependent K+ channels. J Gen Physiol. 1997 Jun;109(6):767–778. doi: 10.1085/jgp.109.6.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Smith P. L., Baukrowitz T., Yellen G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature. 1996 Feb 29;379(6568):833–836. doi: 10.1038/379833a0. [DOI] [PubMed] [Google Scholar]
 - Yang Y., Yan Y., Sigworth F. J. How does the W434F mutation block current in Shaker potassium channels? J Gen Physiol. 1997 Jun;109(6):779–789. doi: 10.1085/jgp.109.6.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Yellen G., Sodickson D., Chen T. Y., Jurman M. E. An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding. Biophys J. 1994 Apr;66(4):1068–1075. doi: 10.1016/S0006-3495(94)80888-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Yellen G. The moving parts of voltage-gated ion channels. Q Rev Biophys. 1998 Aug;31(3):239–295. doi: 10.1017/s0033583598003448. [DOI] [PubMed] [Google Scholar]
 - Zagotta W. N., Aldrich R. W. Voltage-dependent gating of Shaker A-type potassium channels in Drosophila muscle. J Gen Physiol. 1990 Jan;95(1):29–60. doi: 10.1085/jgp.95.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - Zagotta W. N., Hoshi T., Aldrich R. W. Shaker potassium channel gating. III: Evaluation of kinetic models for activation. J Gen Physiol. 1994 Feb;103(2):321–362. doi: 10.1085/jgp.103.2.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
 
