Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1988 Jan;395:455–472. doi: 10.1113/jphysiol.1988.sp016929

Barium-induced automatic activity in isolated ventricular myocytes from guinea-pig hearts.

Y Hirano 1, M Hiraoka 1
PMCID: PMC1192004  PMID: 2457682

Abstract

1. A suction-pipette whole-cell clamp technique was applied to single ventricular myocytes isolated from guinea-pig hearts, in order to investigate the ionic mechanism underlying Ba2+-induced automatic activity. 2. The application of 0.1 mM or less Ba2+ to the myocytes caused a depolarization of the resting membrane potential without inducing spontaneous activity. The stimulated action potential showed a prolonged repolarization phase followed by an after-hyperpolarization. 3. Concentrations of Ba2+ of 0.2 mM or greater produced further depolarization of the resting membrane potential and induced spontaneous activity. Spontaneous activity developed from the slow diastolic depolarization preceded by after-hyperpolarizations of spontaneous or stimulated action potentials. 4. Under voltage-clamp conditions, a decaying outward or inward current in response to hyperpolarizing clamp steps from depolarized potentials appeared in the presence of Ba2+. The Ba2+-induced current decay showed a faster time course with increasing hyperpolarizing clamp pulses and reversed its polarity at around -90 mV, the presumed equilibrium potential for K+ (EK). In the late current-voltage (I-V) relation, Ba2+ almost eliminated the inward-rectifying property. These effects on the cardiac membrane are consistent with a time- and voltage-dependent blocking action of Ba2+ on inward-rectifying K+ currents as reported for other excitable tissues. 5. The concentration- and voltage-dependence of the steady-state block of the inward rectifying K+ current (IK1) was fitted by a simple model assuming 1:1 binding of Ba2+ to a site within the membrane. The apparent dissociation constant at the holding potential of 0 mV (K(0] was 0.3 mM, and the parameter for the membrane potential dependence of Ba2+ blockade (mu) was approximately 0.5. 6. A computer model of the ventricular action potential proposed by Beeler & Reuter (1977) was modified, based on the recent experiments using single cardiac myocytes. The modifications include (1) the current-voltage relationship of IK1, (2) time courses of activation and inactivation of the Ca2+ current (ICa), (3) the activation voltage range for the delayed outward K+ current (IK). 7. The time- and voltage-dependent blocking action of Ba2+ on IK1, including the experimentally determined values for K(0) and mu, were incorporated into the modified version of the action potential model. The computer model reproduced an after-hyperpolarization at doses of Ba2+ lower than 0.1 mM and automatic activity at doses higher than 0.15 mM.(ABSTRACT TRUNCATED AT 400 WORDS)

Full text

PDF
455

Selected References

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

  1. Adelman W. J., Jr, French R. J. Blocking of the squid axon potassium channel by external caesium ions. J Physiol. 1978 Mar;276:13–25. doi: 10.1113/jphysiol.1978.sp012217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antoni H., Oberdisse E. Elektrophysiologische Untersuchungen über die Barium-induzierte Schrittmacher-Aktivität im isolierten Säugetiermyokard. Pflugers Arch Gesamte Physiol Menschen Tiere. 1965 Jun 15;284(3):259–272. [PubMed] [Google Scholar]
  3. Armstrong C. M. Ionic pores, gates, and gating currents. Q Rev Biophys. 1974 May;7(2):179–210. doi: 10.1017/s0033583500001402. [DOI] [PubMed] [Google Scholar]
  4. Bean B. P. Two kinds of calcium channels in canine atrial cells. Differences in kinetics, selectivity, and pharmacology. J Gen Physiol. 1985 Jul;86(1):1–30. doi: 10.1085/jgp.86.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beeler G. W., Reuter H. Reconstruction of the action potential of ventricular myocardial fibres. J Physiol. 1977 Jun;268(1):177–210. doi: 10.1113/jphysiol.1977.sp011853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. DiFrancesco D., Ferroni A., Visentin S. Barium-induced blockade of the inward rectifier in calf Purkinje fibres. Pflugers Arch. 1984 Dec;402(4):446–453. doi: 10.1007/BF00583946. [DOI] [PubMed] [Google Scholar]
  8. DiFrancesco D., Noble D. A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos Trans R Soc Lond B Biol Sci. 1985 Jan 10;307(1133):353–398. doi: 10.1098/rstb.1985.0001. [DOI] [PubMed] [Google Scholar]
  9. Gay L. A., Stanfield P. R. Cs(+) causes a voltage-dependent block of inward K currents in resting skeletal muscle fibres. Nature. 1977 May 12;267(5607):169–170. doi: 10.1038/267169a0. [DOI] [PubMed] [Google Scholar]
  10. Giles W. R., Shibata E. F. Voltage clamp of bull-frog cardiac pace-maker cells: a quantitative analysis of potassium currents. J Physiol. 1985 Nov;368:265–292. doi: 10.1113/jphysiol.1985.sp015857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hagiwara S., Miyazaki S., Moody W., Patlak J. Blocking effects of barium and hydrogen ions on the potassium current during anomalous rectification in the starfish egg. J Physiol. 1978 Jun;279:167–185. doi: 10.1113/jphysiol.1978.sp012338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hagiwara S., Miyazaki S., Rosenthal N. P. Potassium current and the effect of cesium on this current during anomalous rectification of the egg cell membrane of a starfish. J Gen Physiol. 1976 Jun;67(6):621–638. doi: 10.1085/jgp.67.6.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Hille B., Schwarz W. Potassium channels as multi-ion single-file pores. J Gen Physiol. 1978 Oct;72(4):409–442. doi: 10.1085/jgp.72.4.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hirano Y., Hiraoka M. Changes in K+ currents induced by Ba2+ in guinea pig ventricular muscles. Am J Physiol. 1986 Jul;251(1 Pt 2):H24–H33. doi: 10.1152/ajpheart.1986.251.1.H24. [DOI] [PubMed] [Google Scholar]
  16. Hiraoka M., Ikeda K., Sano T. The mechanism of barium-induced automaticity in ventricular muscle fibers. Adv Myocardiol. 1980;1:255–266. [PubMed] [Google Scholar]
  17. Hume J. R., Uehara A. Ionic basis of the different action potential configurations of single guinea-pig atrial and ventricular myocytes. J Physiol. 1985 Nov;368:525–544. doi: 10.1113/jphysiol.1985.sp015874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Imanishi S., Surawicz B. Automatic activity in depolarized guinea pig ventricular myocardium. Characteristics and mechanisms. Circ Res. 1976 Dec;39(6):751–759. doi: 10.1161/01.res.39.6.751. [DOI] [PubMed] [Google Scholar]
  19. Imoto Y., Ehara T., Matsuura H. Voltage- and time-dependent block of iK1 underlying Ba2+-induced ventricular automaticity. Am J Physiol. 1987 Feb;252(2 Pt 2):H325–H333. doi: 10.1152/ajpheart.1987.252.2.H325. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Isenberg G., Klöckner U. Calcium currents of isolated bovine ventricular myocytes are fast and of large amplitude. Pflugers Arch. 1982 Oct;395(1):30–41. doi: 10.1007/BF00584965. [DOI] [PubMed] [Google Scholar]
  22. Jaeger J. M., Gibbons W. R. Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers. Am J Physiol. 1985 Jul;249(1 Pt 2):H122–H132. doi: 10.1152/ajpheart.1985.249.1.H122. [DOI] [PubMed] [Google Scholar]
  23. Kameyama M., Kakei M., Sato R., Shibasaki T., Matsuda H., Irisawa H. Intracellular Na+ activates a K+ channel in mammalian cardiac cells. Nature. 1984 May 24;309(5966):354–356. doi: 10.1038/309354a0. [DOI] [PubMed] [Google Scholar]
  24. Katzung B. G., Morgenstern J. A. Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium. Circ Res. 1977 Jan;40(1):105–111. doi: 10.1161/01.res.40.1.105. [DOI] [PubMed] [Google Scholar]
  25. Kurachi Y. Voltage-dependent activation of the inward-rectifier potassium channel in the ventricular cell membrane of guinea-pig heart. J Physiol. 1985 Sep;366:365–385. doi: 10.1113/jphysiol.1985.sp015803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nakayama T., Kurachi Y., Noma A., Irisawa H. Action potential and membrane currents of single pacemaker cells of the rabbit heart. Pflugers Arch. 1984 Nov;402(3):248–257. doi: 10.1007/BF00585507. [DOI] [PubMed] [Google Scholar]
  27. Nilius B., Hess P., Lansman J. B., Tsien R. W. A novel type of cardiac calcium channel in ventricular cells. Nature. 1985 Aug 1;316(6027):443–446. doi: 10.1038/316443a0. [DOI] [PubMed] [Google Scholar]
  28. Noble D. The surprising heart: a review of recent progress in cardiac electrophysiology. J Physiol. 1984 Aug;353:1–50. doi: 10.1113/jphysiol.1984.sp015320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983 Sep 8;305(5930):147–148. doi: 10.1038/305147a0. [DOI] [PubMed] [Google Scholar]
  30. Noma A., Nakayama T., Kurachi Y., Irisawa H. Resting K conductances in pacemaker and non-pacemaker heart cells of the rabbit. Jpn J Physiol. 1984;34(2):245–254. doi: 10.2170/jjphysiol.34.245. [DOI] [PubMed] [Google Scholar]
  31. Osterrieder W., Yang Q. F., Trautwein W. Effects of barium on the membrane currents in the rabbit S-A node. Pflugers Arch. 1982 Jul;394(1):78–84. doi: 10.1007/BF01108311. [DOI] [PubMed] [Google Scholar]
  32. Reid J. A., Hecht H. H. Barium-induced automaticity in right ventricular muscle in the dog. Circ Res. 1967 Dec;21(6):849–856. doi: 10.1161/01.res.21.6.849. [DOI] [PubMed] [Google Scholar]
  33. Sakmann B., Trube G. Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane. J Physiol. 1984 Feb;347:659–683. doi: 10.1113/jphysiol.1984.sp015089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Standen N. B., Stanfield P. R. A potential- and time-dependent blockade of inward rectification in frog skeletal muscle fibres by barium and strontium ions. J Physiol. 1978 Jul;280:169–191. doi: 10.1113/jphysiol.1978.sp012379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tsien R. W. Calcium channels in excitable cell membranes. Annu Rev Physiol. 1983;45:341–358. doi: 10.1146/annurev.ph.45.030183.002013. [DOI] [PubMed] [Google Scholar]
  36. Woodhull A. M. Ionic blockage of sodium channels in nerve. J Gen Physiol. 1973 Jun;61(6):687–708. doi: 10.1085/jgp.61.6.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yanagihara K., Irisawa H. Potassium current during the pacemaker depolarization in rabbit sinoatrial node cell. Pflugers Arch. 1980 Dec;388(3):255–260. doi: 10.1007/BF00658491. [DOI] [PubMed] [Google Scholar]
  38. Yanagihara K., Noma A., Irisawa H. Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments. Jpn J Physiol. 1980;30(6):841–857. doi: 10.2170/jjphysiol.30.841. [DOI] [PubMed] [Google Scholar]

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

RESOURCES