Skip to main content
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1993 Apr 1;101(4):571–601. doi: 10.1085/jgp.101.4.571

The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. I. Basic characterization and kinetic analysis

PMCID: PMC2216777  PMID: 8505627

Abstract

Enzymatically isolated myocytes from ferret right ventricles (12-16 wk, male) were studied using the whole cell patch clamp technique. The macroscopic properties of a transient outward K+ current I(to) were quantified. I(to) is selective for K+, with a PNa/PK of 0.082. Activation of I(to) is a voltage-dependent process, with both activation and inactivation being independent of Na+ or Ca2+ influx. Steady-state inactivation is well described by a single Boltzmann relationship (V1/2 = -13.5 mV; k = 5.6 mV). Substantial inactivation can occur during a subthreshold depolarization without any measurable macroscopic current. Both development of and recovery from inactivation are well described by single exponential processes. Ensemble averages of single I(to) channel currents recorded in cell-attached patches reproduce macroscopic I(to) and indicate that inactivation is complete at depolarized potentials. The overall inactivation/recovery time constant curve has a bell-shaped potential dependence that peaks between -10 and -20 mV, with time constants (22 degrees C) ranging from 23 ms (-90 mV) to 304 ms (-10 mV). Steady-state activation displays a sigmoidal dependence on membrane potential, with a net aggregate half- activation potential of +22.5 mV. Activation kinetics (0 to +70 mV, 22 degrees C) are rapid, with I(to) peaking in approximately 5-15 ms at +50 mV. Experiments conducted at reduced temperatures (12 degrees C) demonstrate that activation occurs with a time delay. A nonlinear least- squares analysis indicates that three closed kinetic states are necessary and sufficient to model activation. Derived time constants of activation (22 degrees C) ranged from 10 ms (+10 mV) to 2 ms (+70 mV). Within the framework of Hodgkin-Huxley formalism, Ito gating can be described using an a3i formulation.

Full Text

The Full Text of this article is available as a PDF (1.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams D. J., Smith S. J., Thompson S. H. Ionic currents in molluscan soma. Annu Rev Neurosci. 1980;3:141–167. doi: 10.1146/annurev.ne.03.030180.001041. [DOI] [PubMed] [Google Scholar]
  2. Aldrich R. W. Inactivation of voltage-gated delayed potassium current in molluscan neurons. A kinetic model. Biophys J. 1981 Dec;36(3):519–532. doi: 10.1016/S0006-3495(81)84750-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Apkon M., Nerbonne J. M. Alpha 1-adrenergic agonists selectively suppress voltage-dependent K+ current in rat ventricular myocytes. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8756–8760. doi: 10.1073/pnas.85.22.8756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Apkon M., Nerbonne J. M. Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes. J Gen Physiol. 1991 May;97(5):973–1011. doi: 10.1085/jgp.97.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Braun A. P., Fedida D., Clark R. B., Giles W. R. Intracellular mechanisms for alpha 1-adrenergic regulation of the transient outward current in rabbit atrial myocytes. J Physiol. 1990 Dec;431:689–712. doi: 10.1113/jphysiol.1990.sp018355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Callewaert G., Vereecke J., Carmeliet E. Existence of a calcium-dependent potassium channel in the membrane of cow cardiac Purkinje cells. Pflugers Arch. 1986 Apr;406(4):424–426. doi: 10.1007/BF00590947. [DOI] [PubMed] [Google Scholar]
  10. Campbell D. L., Giles W. R., Robinson K., Shibata E. F. Studies of the sodium-calcium exchanger in bull-frog atrial myocytes. J Physiol. 1988 Sep;403:317–340. doi: 10.1113/jphysiol.1988.sp017251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Campbell D. L., Qu Y., Rasmusson R. L., Strauss H. C. The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. II. Closed state reverse use-dependent block by 4-aminopyridine. J Gen Physiol. 1993 Apr;101(4):603–626. doi: 10.1085/jgp.101.4.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Campbell D. L., Rasmusson R. L., Strauss H. C. Ionic current mechanisms generating vertebrate primary cardiac pacemaker activity at the single cell level: an integrative view. Annu Rev Physiol. 1992;54:279–302. doi: 10.1146/annurev.ph.54.030192.001431. [DOI] [PubMed] [Google Scholar]
  13. Clark R. B., Giles W. R., Imaizumi Y. Properties of the transient outward current in rabbit atrial cells. J Physiol. 1988 Nov;405:147–168. doi: 10.1113/jphysiol.1988.sp017326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Connor J. A., Stevens C. F. Voltage clamp studies of a transient outward membrane current in gastropod neural somata. J Physiol. 1971 Feb;213(1):21–30. doi: 10.1113/jphysiol.1971.sp009365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. DeCoursey T. E. State-dependent inactivation of K+ currents in rat type II alveolar epithelial cells. J Gen Physiol. 1990 Apr;95(4):617–646. doi: 10.1085/jgp.95.4.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Denyer J. C., Brown H. F. Rabbit sino-atrial node cells: isolation and electrophysiological properties. J Physiol. 1990 Sep;428:405–424. doi: 10.1113/jphysiol.1990.sp018219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Duchatelle-Gourdon I., Hartzell H. C., Lagrutta A. A. Modulation of the delayed rectifier potassium current in frog cardiomyocytes by beta-adrenergic agonists and magnesium. J Physiol. 1989 Aug;415:251–274. doi: 10.1113/jphysiol.1989.sp017721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Dukes I. D., Morad M. The transient K+ current in rat ventricular myocytes: evaluation of its Ca2+ and Na+ dependence. J Physiol. 1991 Apr;435:395–420. doi: 10.1113/jphysiol.1991.sp018516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fedida D., Shimoni Y., Giles W. R. Alpha-adrenergic modulation of the transient outward current in rabbit atrial myocytes. J Physiol. 1990 Apr;423:257–277. doi: 10.1113/jphysiol.1990.sp018021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gabella G. Inpocketings of the cell membrane (caveolae) in the rat myocardium. J Ultrastruct Res. 1978 Nov;65(2):135–147. doi: 10.1016/s0022-5320(78)90051-5. [DOI] [PubMed] [Google Scholar]
  21. Giles W. R., Imaizumi Y. Comparison of potassium currents in rabbit atrial and ventricular cells. J Physiol. 1988 Nov;405:123–145. doi: 10.1113/jphysiol.1988.sp017325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Giles W. R., van Ginneken A. C. A transient outward current in isolated cells from the crista terminalis of rabbit heart. J Physiol. 1985 Nov;368:243–264. doi: 10.1113/jphysiol.1985.sp015856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gotoh Y., Imaizumi Y., Watanabe M., Shibata E. F., Clark R. B., Giles W. R. Inhibition of transient outward K+ current by DHP Ca2+ antagonists and agonists in rabbit cardiac myocytes. Am J Physiol. 1991 May;260(5 Pt 2):H1737–H1742. doi: 10.1152/ajpheart.1991.260.5.H1737. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  27. Harvey R. D., Ten Eick R. E. Characterization of the inward-rectifying potassium current in cat ventricular myocytes. J Gen Physiol. 1988 Apr;91(4):593–615. doi: 10.1085/jgp.91.4.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hille B. Ionic channels in excitable membranes. Current problems and biophysical approaches. Biophys J. 1978 May;22(2):283–294. doi: 10.1016/S0006-3495(78)85489-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hiraoka M., Kawano S. Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes. J Physiol. 1989 Mar;410:187–212. doi: 10.1113/jphysiol.1989.sp017528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hondeghem L. M., Snyders D. J. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation. 1990 Feb;81(2):686–690. doi: 10.1161/01.cir.81.2.686. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Hume J. R., Giles W., Robinson K., Shibata E. F., Nathan R. D., Kanai K., Rasmusson R. A time- and voltage-dependent K+ current in single cardiac cells from bullfrog atrium. J Gen Physiol. 1986 Dec;88(6):777–798. doi: 10.1085/jgp.88.6.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hume J. R., Uehara A., Hadley R. W., Harvey R. D. Comparison of K+ channels in mammalian atrial and ventricular myocytes. Prog Clin Biol Res. 1990;334:17–41. [PubMed] [Google Scholar]
  34. Imaizumi Y., Giles W. R. Quinidine-induced inhibition of transient outward current in cardiac muscle. Am J Physiol. 1987 Sep;253(3 Pt 2):H704–H708. doi: 10.1152/ajpheart.1987.253.3.H704. [DOI] [PubMed] [Google Scholar]
  35. Jan L. Y., Jan Y. N. Structural elements involved in specific K+ channel functions. Annu Rev Physiol. 1992;54:537–555. doi: 10.1146/annurev.ph.54.030192.002541. [DOI] [PubMed] [Google Scholar]
  36. Josephson I. R., Sanchez-Chapula J., Brown A. M. Early outward current in rat single ventricular cells. Circ Res. 1984 Feb;54(2):157–162. doi: 10.1161/01.res.54.2.157. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Lefevre I. A., Coulombe A., Coraboeuf E. The calcium antagonist D600 inhibits calcium-independent transient outward current in isolated rat ventricular myocytes. J Physiol. 1991 Jan;432:65–80. doi: 10.1113/jphysiol.1991.sp018376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Miller C. 1990: annus mirabilis of potassium channels. Science. 1991 May 24;252(5009):1092–1096. doi: 10.1126/science.252.5009.1092. [DOI] [PubMed] [Google Scholar]
  41. Nakayama T., Irisawa H. Transient outward current carried by potassium and sodium in quiescent atrioventricular node cells of rabbits. Circ Res. 1985 Jul;57(1):65–73. doi: 10.1161/01.res.57.1.65. [DOI] [PubMed] [Google Scholar]
  42. Nathan R. D. Two electrophysiologically distinct types of cultured pacemaker cells from rabbit sinoatrial node. Am J Physiol. 1986 Feb;250(2 Pt 2):H325–H329. doi: 10.1152/ajpheart.1986.250.2.H325. [DOI] [PubMed] [Google Scholar]
  43. Neher E. Two fast transient current components during voltage clamp on snail neurons. J Gen Physiol. 1971 Jul;58(1):36–53. doi: 10.1085/jgp.58.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Patlak J. Molecular kinetics of voltage-dependent Na+ channels. Physiol Rev. 1991 Oct;71(4):1047–1080. doi: 10.1152/physrev.1991.71.4.1047. [DOI] [PubMed] [Google Scholar]
  45. Rudy B. Diversity and ubiquity of K channels. Neuroscience. 1988 Jun;25(3):729–749. doi: 10.1016/0306-4522(88)90033-4. [DOI] [PubMed] [Google Scholar]
  46. Sanguinetti M. C., Jurkiewicz N. K. Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol. 1990 Jul;96(1):195–215. doi: 10.1085/jgp.96.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sanguinetti M. C. Na+1-activated and ATP-sensitive K+ channels in the heart. Prog Clin Biol Res. 1990;334:85–109. [PubMed] [Google Scholar]
  48. Shibata E. F., Drury T., Refsum H., Aldrete V., Giles W. Contributions of a transient outward current to repolarization in human atrium. Am J Physiol. 1989 Dec;257(6 Pt 2):H1773–H1781. doi: 10.1152/ajpheart.1989.257.6.H1773. [DOI] [PubMed] [Google Scholar]
  49. Solc C. K., Aldrich R. W. Gating of single non-Shaker A-type potassium channels in larval Drosophila neurons. J Gen Physiol. 1990 Jul;96(1):135–165. doi: 10.1085/jgp.96.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Solc C. K., Zagotta W. N., Aldrich R. W. Single-channel and genetic analyses reveal two distinct A-type potassium channels in Drosophila. Science. 1987 May 29;236(4805):1094–1098. doi: 10.1126/science.2437657. [DOI] [PubMed] [Google Scholar]
  51. Sorota S. Swelling-induced chloride-sensitive current in canine atrial cells revealed by whole-cell patch-clamp method. Circ Res. 1992 Apr;70(4):679–687. doi: 10.1161/01.res.70.4.679. [DOI] [PubMed] [Google Scholar]
  52. Tseng G. N., Hoffman B. F. Two components of transient outward current in canine ventricular myocytes. Circ Res. 1989 Apr;64(4):633–647. doi: 10.1161/01.res.64.4.633. [DOI] [PubMed] [Google Scholar]
  53. 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]
  54. 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]
  55. Zagotta W. N., Brainard M. S., Aldrich R. W. Single-channel analysis of four distinct classes of potassium channels in Drosophila muscle. J Neurosci. 1988 Dec;8(12):4765–4779. doi: 10.1523/JNEUROSCI.08-12-04765.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. 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]

Articles from The Journal of General Physiology are provided here courtesy of The Rockefeller University Press

RESOURCES