Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1994 Jun 15;477(Pt 3):423–435. doi: 10.1113/jphysiol.1994.sp020204

Cation-dependent gating of the hyperpolarization-activated cation current in the rabbit sino-atrial node cells.

F Maruoka 1, Y Nakashima 1, M Takano 1, K Ono 1, A Noma 1
PMCID: PMC1155607  PMID: 7932232

Abstract

1. The gating properties of the hyperpolarization-activated cation current (I(f) or Ih) were investigated in single pacemaker cells dissociated from the rabbit sino-atrial node. 2. The whole-cell I(f) was recorded in the presence of different external cations. The inward I(f) was increased when external Na+ was replaced with K+, and was decreased in Li+ or Rb+ solution. In Tris+ and Cs+ solutions, the inward I(f) was negligible. The outward tail current recorded upon depolarization was largest in Li+ solution and smaller in a sequence of Na+, Tris+ and K+ solutions. In Rb+ and Cs+ solutions, only a small tail current was recorded. 3. The outward tail current had a 'shoulder' in Na+ solution, which was much delayed by replacing Na+ with Li+. In K+ solution, the decay of the tail current was much faster, and no obvious shoulder was recorded. The tail current was slowest in Li(+)-rich and 0 mM K+ solution, and was progressively accelerated by adding K+ over the range from 0 to 3 mM. The tail current at 30 mM [K+]o showed only a small shoulder. A common binding site to modulate the I(f) deactivation was suggested for monovalent cations. 4. The shoulder of the I(f) tail became more evident as I(f) was activated to a larger extent either by prolonging the duration or by increasing the amplitude of the preceding hyperpolarization in both Na+ and Li+ solutions. 5. The I(f) was first activated by hyperpolarizing the membrane to -110 mV, and then deactivated by depolarization. The inward tail current at -50 mV showed a single exponential decay. At more positive potentials, the shoulder of the outward tail currents became more evident and the rate of the final decay was increased. 6. The time course of I(f) activation was well fitted with the sum of two exponential functions. Time constants of both components were not affected by the external cation (Na+, K+ or Li+) replacement. Likewise, the quasi-steady state activation was conserved when external Na+ was replaced with Li+. 7. Two closed and three open states were assumed in a sequential state model of the I(f) channel. The cation effects were well simulated by assuming that the deactivation rate was selectively modulated. The flow of I(f) during the spontaneous action potential was calculated. The activation of I(f) started on repolarization to the maximum diastolic potential and reached a maximum in the middle of the diastolic period. Its peak amplitude was 14% of the net inward current during the diastolic period.

Full text

PDF
423

Selected References

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

  1. 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]
  2. Begenisich T. B., Cahalan M. D. Sodium channel permeation in squid axons. I: Reversal potential experiments. J Physiol. 1980 Oct;307:217–242. doi: 10.1113/jphysiol.1980.sp013432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Denyer J. C., Brown H. F. Pacemaking in rabbit isolated sino-atrial node cells during Cs+ block of the hyperpolarization-activated current if. J Physiol. 1990 Oct;429:401–409. doi: 10.1113/jphysiol.1990.sp018264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. DiFrancesco D. A new interpretation of the pace-maker current in calf Purkinje fibres. J Physiol. 1981 May;314:359–376. doi: 10.1113/jphysiol.1981.sp013713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DiFrancesco D. A study of the ionic nature of the pace-maker current in calf Purkinje fibres. J Physiol. 1981 May;314:377–393. doi: 10.1113/jphysiol.1981.sp013714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DiFrancesco D. Block and activation of the pace-maker channel in calf purkinje fibres: effects of potassium, caesium and rubidium. J Physiol. 1982 Aug;329:485–507. doi: 10.1113/jphysiol.1982.sp014315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DiFrancesco D. Characterization of single pacemaker channels in cardiac sino-atrial node cells. Nature. 1986 Dec 4;324(6096):470–473. doi: 10.1038/324470a0. [DOI] [PubMed] [Google Scholar]
  9. DiFrancesco D. Characterization of the pace-maker current kinetics in calf Purkinje fibres. J Physiol. 1984 Mar;348:341–367. doi: 10.1113/jphysiol.1984.sp015114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DiFrancesco D., Ducouret P., Robinson R. B. Muscarinic modulation of cardiac rate at low acetylcholine concentrations. Science. 1989 Feb 3;243(4891):669–671. doi: 10.1126/science.2916119. [DOI] [PubMed] [Google Scholar]
  11. DiFrancesco D., Ferroni A. Delayed activation of the cardiac pacemaker current and its dependence on conditioning pre-hyperpolarizations. Pflugers Arch. 1983 Mar 1;396(3):265–267. doi: 10.1007/BF00587866. [DOI] [PubMed] [Google Scholar]
  12. DiFrancesco D., Ferroni A., Mazzanti M., Tromba C. Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node. J Physiol. 1986 Aug;377:61–88. doi: 10.1113/jphysiol.1986.sp016177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. DiFrancesco D., Porciatti F., Janigro D., Maccaferri G., Mangoni M., Tritella T., Chang F., Cohen I. S. Block of the cardiac pacemaker current (If) in the rabbit sino-atrial node and in canine Purkinje fibres by 9-amino-1,2,3,4-tetrahydroacridine. Pflugers Arch. 1991 Feb;417(6):611–615. doi: 10.1007/BF00372959. [DOI] [PubMed] [Google Scholar]
  14. DiFrancesco D. The contribution of the 'pacemaker' current (if) to generation of spontaneous activity in rabbit sino-atrial node myocytes. J Physiol. 1991 Mar;434:23–40. doi: 10.1113/jphysiol.1991.sp018457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. DiFrancesco D., Tromba C. Inhibition of the hyperpolarization-activated current (if) induced by acetylcholine in rabbit sino-atrial node myocytes. J Physiol. 1988 Nov;405:477–491. doi: 10.1113/jphysiol.1988.sp017343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. DiFrancesco D., Tromba C. Muscarinic control of the hyperpolarization-activated current (if) in rabbit sino-atrial node myocytes. J Physiol. 1988 Nov;405:493–510. doi: 10.1113/jphysiol.1988.sp017344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Eckert R., Chad J. E. Inactivation of Ca channels. Prog Biophys Mol Biol. 1984;44(3):215–267. doi: 10.1016/0079-6107(84)90009-9. [DOI] [PubMed] [Google Scholar]
  18. Frace A. M., Maruoka F., Noma A. Control of the hyperpolarization-activated cation current by external anions in rabbit sino-atrial node cells. J Physiol. 1992;453:307–318. doi: 10.1113/jphysiol.1992.sp019230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Frace A. M., Maruoka F., Noma A. External K+ increases Na+ conductance of the hyperpolarization-activated current in rabbit cardiac pacemaker cells. Pflugers Arch. 1992 Jun;421(2-3):97–99. [PubMed] [Google Scholar]
  20. Hagiwara N., Irisawa H. Modulation by intracellular Ca2+ of the hyperpolarization-activated inward current in rabbit single sino-atrial node cells. J Physiol. 1989 Feb;409:121–141. doi: 10.1113/jphysiol.1989.sp017488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hagiwara S., Miyazaki S., Krasne S., Ciani S. Anomalous permeabilities of the egg cell membrane of a starfish in K+-Tl+ mixtures. J Gen Physiol. 1977 Sep;70(3):269–281. doi: 10.1085/jgp.70.3.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hagiwara S., Yoshii M. Effects of internal potassium and sodium on the anomalous rectification of the starfish egg as examined by internal perfusion. J Physiol. 1979 Jul;292:251–265. doi: 10.1113/jphysiol.1979.sp012849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Hess P., Tsien R. W. Mechanism of ion permeation through calcium channels. 1984 May 31-Jun 6Nature. 309(5967):453–456. doi: 10.1038/309453a0. [DOI] [PubMed] [Google Scholar]
  25. Hestrin S. The properties and function of inward rectification in rod photoreceptors of the tiger salamander. J Physiol. 1987 Sep;390:319–333. doi: 10.1113/jphysiol.1987.sp016703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Irisawa H., Brown H. F., Giles W. Cardiac pacemaking in the sinoatrial node. Physiol Rev. 1993 Jan;73(1):197–227. doi: 10.1152/physrev.1993.73.1.197. [DOI] [PubMed] [Google Scholar]
  27. Isenberg G., Klockner U. Calcium tolerant ventricular myocytes prepared by preincubation in a "KB medium". Pflugers Arch. 1982 Oct;395(1):6–18. doi: 10.1007/BF00584963. [DOI] [PubMed] [Google Scholar]
  28. Leech C. A., Stanfield P. R. Inward rectification in frog skeletal muscle fibres and its dependence on membrane potential and external potassium. J Physiol. 1981;319:295–309. doi: 10.1113/jphysiol.1981.sp013909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McCormick D. A., Pape H. C. Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurones. J Physiol. 1990 Dec;431:291–318. doi: 10.1113/jphysiol.1990.sp018331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Noma A., Morad M., Irisawa H. Does the "pacemaker current" generate the diastolic depolarization in the rabbit SA node cells? Pflugers Arch. 1983 May;397(3):190–194. doi: 10.1007/BF00584356. [DOI] [PubMed] [Google Scholar]
  31. Saigusa A., Matsuda H. Outward currents through the inwardly rectifying potassium channel of guinea-pig ventricular cells. Jpn J Physiol. 1988;38(1):77–91. doi: 10.2170/jjphysiol.38.77. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Wollmuth L. P., Hille B. Ionic selectivity of Ih channels of rod photoreceptors in tiger salamanders. J Gen Physiol. 1992 Nov;100(5):749–765. doi: 10.1085/jgp.100.5.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yanagihara K., Irisawa H. Inward current activated during hyperpolarization in the rabbit sinoatrial node cell. Pflugers Arch. 1980 May;385(1):11–19. doi: 10.1007/BF00583909. [DOI] [PubMed] [Google Scholar]
  36. Yatani A., Brown A. M. Regulation of cardiac pacemaker current If in excised membranes from sinoatrial node cells. Am J Physiol. 1990 Jun;258(6 Pt 2):H1947–H1951. doi: 10.1152/ajpheart.1990.258.6.H1947. [DOI] [PubMed] [Google Scholar]
  37. Zaza A., Maccaferri G., Mangoni M., DiFrancesco D. Intracellular calcium does not directly modulate cardiac pacemaker (if) channels. Pflugers Arch. 1991 Dec;419(6):662–664. doi: 10.1007/BF00370312. [DOI] [PubMed] [Google Scholar]
  38. van Ginneken A. C., Giles W. Voltage clamp measurements of the hyperpolarization-activated inward current I(f) in single cells from rabbit sino-atrial node. J Physiol. 1991 Mar;434:57–83. doi: 10.1113/jphysiol.1991.sp018459. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES