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. 1994 Feb 1;103(2):321–362. doi: 10.1085/jgp.103.2.321

Shaker potassium channel gating. III: Evaluation of kinetic models for activation

PMCID: PMC2216839  PMID: 8189208

Abstract

Predictions of different classes of gating models involving identical conformational changes in each of four subunits were compared to the gating behavior of Shaker potassium channels without N-type inactivation. Each model was tested to see if it could simulate the voltage dependence of the steady state open probability, and the kinetics of the single-channel currents, macroscopic ionic currents and macroscopic gating currents using a single set of parameters. Activation schemes based upon four identical single-step activation processes were found to be incompatible with the experimental results, as were those involving a concerted, opening transition. A model where the opening of the channel requires two conformational changes in each of the four subunits can adequately account for the steady state and kinetic behavior of the channel. In this model, the gating in each subunit is independent except for a stabilization of the open state when all four subunits are activated, and an unstable closed conformation that the channel enters after opening. A small amount of negative cooperativity between the subunits must be added to account quantitatively for the dependence of the activation time course on holding voltage.

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Selected References

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  1. Alicata D. A., Rayner M. D., Starkus J. G. Osmotic and pharmacological effects of formamide on capacity current, gating current, and sodium current in crayfish giant axons. Biophys J. 1989 Feb;55(2):347–353. doi: 10.1016/S0006-3495(89)82811-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alicata D. A., Rayner M. D., Starkus J. G. Sodium channel activation mechanisms. Insights from deuterium oxide substitution. Biophys J. 1990 Apr;57(4):745–758. doi: 10.1016/S0006-3495(90)82595-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Almers W. Gating currents and charge movements in excitable membranes. Rev Physiol Biochem Pharmacol. 1978;82:96–190. doi: 10.1007/BFb0030498. [DOI] [PubMed] [Google Scholar]
  4. Andersen O. S., Koeppe R. E., 2nd Molecular determinants of channel function. Physiol Rev. 1992 Oct;72(4 Suppl):S89–158. doi: 10.1152/physrev.1992.72.suppl_4.S89. [DOI] [PubMed] [Google Scholar]
  5. Armstrong C. M., Bezanilla F. Charge movement associated with the opening and closing of the activation gates of the Na channels. J Gen Physiol. 1974 May;63(5):533–552. doi: 10.1085/jgp.63.5.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Armstrong C. M. Sodium channels and gating currents. Physiol Rev. 1981 Jul;61(3):644–683. doi: 10.1152/physrev.1981.61.3.644. [DOI] [PubMed] [Google Scholar]
  7. Ascher P., Marty A., Neild T. O. Life time and elementary conductance of the channels mediating the excitatory effects of acetylcholine in Aplysia neurones. J Physiol. 1978 May;278:177–206. doi: 10.1113/jphysiol.1978.sp012299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Auerbach A. A statistical analysis of acetylcholine receptor activation in Xenopus myocytes: stepwise versus concerted models of gating. J Physiol. 1993 Feb;461:339–378. doi: 10.1113/jphysiol.1993.sp019517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bezanilla F., Perozo E., Papazian D. M., Stefani E. Molecular basis of gating charge immobilization in Shaker potassium channels. Science. 1991 Nov 1;254(5032):679–683. doi: 10.1126/science.1948047. [DOI] [PubMed] [Google Scholar]
  10. Blatz A. L., Magleby K. L. Correcting single channel data for missed events. Biophys J. 1986 May;49(5):967–980. doi: 10.1016/S0006-3495(86)83725-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. COLE K. S., MOORE J. W. Potassium ion current in the squid giant axon: dynamic characteristic. Biophys J. 1960 Sep;1:1–14. doi: 10.1016/s0006-3495(60)86871-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Gautam M., Tanouye M. A. Alteration of potassium channel gating: molecular analysis of the Drosophila Sh5 mutation. Neuron. 1990 Jul;5(1):67–73. doi: 10.1016/0896-6273(90)90034-d. [DOI] [PubMed] [Google Scholar]
  14. Gilly W. F., Armstrong C. M. Divalent cations and the activation kinetics of potassium channels in squid giant axons. J Gen Physiol. 1982 Jun;79(6):965–996. doi: 10.1085/jgp.79.6.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hill T. L., Chen Y. D. On the theory of ion transport across the nerve membrane. 3. Potassium ion kinetics and cooperativity (with x=4,6,9). Proc Natl Acad Sci U S A. 1971 Oct;68(10):2488–2492. doi: 10.1073/pnas.68.10.2488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hill T. L., Chen Y. D. On the theory of ion transport across the nerve membrane. II. Potassium ion kinetics and cooperativity (with x = 4). Proc Natl Acad Sci U S A. 1971 Aug;68(8):1711–1715. doi: 10.1073/pnas.68.8.1711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Hurst R. S., Kavanaugh M. P., Yakel J., Adelman J. P., North R. A. Cooperative interactions among subunits of a voltage-dependent potassium channel. Evidence from expression of concatenated cDNAs. J Biol Chem. 1992 Nov 25;267(33):23742–23745. [PubMed] [Google Scholar]
  22. Keynes R. D., Greeff N. G., Forster I. C. Kinetic analysis of the sodium gating current in the squid giant axon. Proc R Soc Lond B Biol Sci. 1990 Jun 22;240(1299):411–423. doi: 10.1098/rspb.1990.0045. [DOI] [PubMed] [Google Scholar]
  23. Keynes R. D. On the voltage dependence of inactivation in the sodium channel of the squid giant axon. Proc Biol Sci. 1991 Jan 22;243(1306):47–53. doi: 10.1098/rspb.1991.0008. [DOI] [PubMed] [Google Scholar]
  24. Koren G., Liman E. R., Logothetis D. E., Nadal-Ginard B., Hess P. Gating mechanism of a cloned potassium channel expressed in frog oocytes and mammalian cells. Neuron. 1990 Jan;4(1):39–51. doi: 10.1016/0896-6273(90)90442-i. [DOI] [PubMed] [Google Scholar]
  25. Lichtinghagen R., Stocker M., Wittka R., Boheim G., Stühmer W., Ferrus A., Pongs O. Molecular basis of altered excitability in Shaker mutants of Drosophila melanogaster. EMBO J. 1990 Dec;9(13):4399–4407. doi: 10.1002/j.1460-2075.1990.tb07890.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Liman E. R., Hess P., Weaver F., Koren G. Voltage-sensing residues in the S4 region of a mammalian K+ channel. Nature. 1991 Oct 24;353(6346):752–756. doi: 10.1038/353752a0. [DOI] [PubMed] [Google Scholar]
  27. Lopez G. A., Jan Y. N., Jan L. Y. Hydrophobic substitution mutations in the S4 sequence alter voltage-dependent gating in Shaker K+ channels. Neuron. 1991 Aug;7(2):327–336. doi: 10.1016/0896-6273(91)90271-z. [DOI] [PubMed] [Google Scholar]
  28. MONOD J., WYMAN J., CHANGEUX J. P. ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. J Mol Biol. 1965 May;12:88–118. doi: 10.1016/s0022-2836(65)80285-6. [DOI] [PubMed] [Google Scholar]
  29. MacKinnon R. Determination of the subunit stoichiometry of a voltage-activated potassium channel. Nature. 1991 Mar 21;350(6315):232–235. doi: 10.1038/350232a0. [DOI] [PubMed] [Google Scholar]
  30. Marchais D., Marty A. Interaction of permeant ions with channels activated by acetylcholine in Aplysia neurones. J Physiol. 1979 Dec;297(0):9–45. doi: 10.1113/jphysiol.1979.sp013025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Marks T. N., Jones S. W. Calcium currents in the A7r5 smooth muscle-derived cell line. An allosteric model for calcium channel activation and dihydropyridine agonist action. J Gen Physiol. 1992 Mar;99(3):367–390. doi: 10.1085/jgp.99.3.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Matteson D. R., Swenson R. P., Jr External monovalent cations that impede the closing of K channels. J Gen Physiol. 1986 May;87(5):795–816. doi: 10.1085/jgp.87.5.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. McCormack K., Tanouye M. A., Iverson L. E., Lin J. W., Ramaswami M., McCormack T., Campanelli J. T., Mathew M. K., Rudy B. A role for hydrophobic residues in the voltage-dependent gating of Shaker K+ channels. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2931–2935. doi: 10.1073/pnas.88.7.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. McManus O. B., Magleby K. L. Kinetic time constants independent of previous single-channel activity suggest Markov gating for a large conductance Ca-activated K channel. J Gen Physiol. 1989 Dec;94(6):1037–1070. doi: 10.1085/jgp.94.6.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. McManus O. B., Spivak C. E., Blatz A. L., Weiss D. S., Magleby K. L. Fractal models, Markov models, and channel kinetics. Biophys J. 1989 Feb;55(2):383–385. doi: 10.1016/S0006-3495(89)82817-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Papazian D. M., Timpe L. C., Jan Y. N., Jan L. Y. Alteration of voltage-dependence of Shaker potassium channel by mutations in the S4 sequence. Nature. 1991 Jan 24;349(6307):305–310. doi: 10.1038/349305a0. [DOI] [PubMed] [Google Scholar]
  37. Perozo E., Papazian D. M., Stefani E., Bezanilla F. Gating currents in Shaker K+ channels. Implications for activation and inactivation models. Biophys J. 1992 Apr;62(1):160–171. doi: 10.1016/S0006-3495(92)81802-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rayner M. D., Starkus J. G., Ruben P. C., Alicata D. A. Voltage-sensitive and solvent-sensitive processes in ion channel gating. Kinetic effects of hyperosmolar media on activation and deactivation of sodium channels. Biophys J. 1992 Jan;61(1):96–108. doi: 10.1016/S0006-3495(92)81819-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sala S., Matteson D. R. Voltage-dependent slowing of K channel closing kinetics by Rb+. J Gen Physiol. 1991 Sep;98(3):535–554. doi: 10.1085/jgp.98.3.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schauf C. L., Bullock J. O. Modifications of sodium channel gating in Myxicola giant axons by deuterium oxide, temperature, and internal cations. Biophys J. 1979 Aug;27(2):193–208. doi: 10.1016/S0006-3495(79)85211-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schauf C. L., Bullock J. O. Solvent substitution as a probe of channel gating in Myxicola. Differential effects of D2O on some components of membrane conductance. Biophys J. 1980 May;30(2):295–305. doi: 10.1016/S0006-3495(80)85095-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Schauf C. L., Bullock J. O. Solvent substitution as a probe of channel gating in Myxicola. Effects of D2O on kinetic properties of drugs that occlude channels. Biophys J. 1982 Feb;37(2):441–452. doi: 10.1016/S0006-3495(82)84690-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Schoppa N. E., McCormack K., Tanouye M. A., Sigworth F. J. The size of gating charge in wild-type and mutant Shaker potassium channels. Science. 1992 Mar 27;255(5052):1712–1715. doi: 10.1126/science.1553560. [DOI] [PubMed] [Google Scholar]
  44. Shapiro M. S., DeCoursey T. E. Permeant ion effects on the gating kinetics of the type L potassium channel in mouse lymphocytes. J Gen Physiol. 1991 Jun;97(6):1251–1278. doi: 10.1085/jgp.97.6.1251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Shapiro M. S., DeCoursey T. E. Selectivity and gating of the type L potassium channel in mouse lymphocytes. J Gen Physiol. 1991 Jun;97(6):1227–1250. doi: 10.1085/jgp.97.6.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sine S. M., Claudio T., Sigworth F. J. Activation of Torpedo acetylcholine receptors expressed in mouse fibroblasts. Single channel current kinetics reveal distinct agonist binding affinities. J Gen Physiol. 1990 Aug;96(2):395–437. doi: 10.1085/jgp.96.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Spruce A. E., Standen N. B., Stanfield P. R. Rubidium ions and the gating of delayed rectifier potassium channels of frog skeletal muscle. J Physiol. 1989 Apr;411:597–610. doi: 10.1113/jphysiol.1989.sp017593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Stevens C. F. Interactions between intrinsic membrane protein and electric field. An approach to studying nerve excitability. Biophys J. 1978 May;22(2):295–306. doi: 10.1016/S0006-3495(78)85490-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Stühmer W., Conti F., Stocker M., Pongs O., Heinemann S. H. Gating currents of inactivating and non-inactivating potassium channels expressed in Xenopus oocytes. Pflugers Arch. 1991 May;418(4):423–429. doi: 10.1007/BF00550881. [DOI] [PubMed] [Google Scholar]
  50. Stühmer W., Conti F., Suzuki H., Wang X. D., Noda M., Yahagi N., Kubo H., Numa S. Structural parts involved in activation and inactivation of the sodium channel. Nature. 1989 Jun 22;339(6226):597–603. doi: 10.1038/339597a0. [DOI] [PubMed] [Google Scholar]
  51. Swenson R. P., Jr, Armstrong C. M. K+ channels close more slowly in the presence of external K+ and Rb+. Nature. 1981 Jun 4;291(5814):427–429. doi: 10.1038/291427a0. [DOI] [PubMed] [Google Scholar]
  52. Tanabe T., Adams B. A., Numa S., Beam K. G. Repeat I of the dihydropyridine receptor is critical in determining calcium channel activation kinetics. Nature. 1991 Aug 29;352(6338):800–803. doi: 10.1038/352800a0. [DOI] [PubMed] [Google Scholar]
  53. Tytgat J., Hess P. Evidence for cooperative interactions in potassium channel gating. Nature. 1992 Oct 1;359(6394):420–423. doi: 10.1038/359420a0. [DOI] [PubMed] [Google Scholar]
  54. Vandenberg C. A., Bezanilla F. A sodium channel gating model based on single channel, macroscopic ionic, and gating currents in the squid giant axon. Biophys J. 1991 Dec;60(6):1511–1533. doi: 10.1016/S0006-3495(91)82186-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. White M. M., Bezanilla F. Activation of squid axon K+ channels. Ionic and gating current studies. J Gen Physiol. 1985 Apr;85(4):539–554. doi: 10.1085/jgp.85.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Young S. H., Moore J. W. Potassium ion currents in the crayfish giant axon. Dynamic characteristics. Biophys J. 1981 Dec;36(3):723–733. doi: 10.1016/S0006-3495(81)84761-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Zagotta W. N., Aldrich R. W. Alterations in activation gating of single Shaker A-type potassium channels by the Sh5 mutation. J Neurosci. 1990 Jun;10(6):1799–1810. doi: 10.1523/JNEUROSCI.10-06-01799.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. 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]
  59. Zagotta W. N., Hoshi T., Aldrich R. W. Gating of single Shaker potassium channels in Drosophila muscle and in Xenopus oocytes injected with Shaker mRNA. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7243–7247. doi: 10.1073/pnas.86.18.7243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Zagotta W. N., Hoshi T., Aldrich R. W. Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB. Science. 1990 Oct 26;250(4980):568–571. doi: 10.1126/science.2122520. [DOI] [PubMed] [Google Scholar]
  61. Zagotta W. N., Hoshi T., Dittman J., Aldrich R. W. Shaker potassium channel gating. II: Transitions in the activation pathway. J Gen Physiol. 1994 Feb;103(2):279–319. doi: 10.1085/jgp.103.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Zimmerberg J., Bezanilla F., Parsegian V. A. Solute inaccessible aqueous volume changes during opening of the potassium channel of the squid giant axon. Biophys J. 1990 May;57(5):1049–1064. doi: 10.1016/S0006-3495(90)82623-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

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