Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1987 Oct;391:169–191. doi: 10.1113/jphysiol.1987.sp016732

Calcium current in isolated neonatal rat ventricular myocytes.

N M Cohen 1, W J Lederer 1
PMCID: PMC1192208  PMID: 2451004

Abstract

1. Calcium currents (ICa) from neonatal rat ventricular heart muscle cells grown in primary culture were examined using the 'whole-cell' voltage-clamp technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). Examination of ICa was limited to one calcium channel type, 'L' type (Nilius, Hess, Lansman & Tsien, 1985), by appropriate voltage protocols. 2. We measured transient and steady-state components of ICa, and could generally describe ICa in terms of the steady-state activation (d infinity) and inactivation (f infinity) parameters. 3. We observed that the reduction of ICa by the calcium channel antagonist D600 can be explained by both a shift of d infinity to more positive potentials as well as a slight reduction of ICa conductance. D600 did not significantly alter either the rate of inactivation of ICa or the voltage dependence of f infinity. 4. The calcium channel modulator BAY K8644 shifted both d infinity and f infinity to more negative potentials. Additionally, BAY K8644 increased the rate of inactivation at potentials between +5 and +55 mV. Furthermore, BAY K8644 also increased ICa conductance, a change consistent with a promotion of 'mode 2' calcium channel activity (Hess, Lansman & Tsien, 1984). 5. We conclude that, as predicted by d infinity and f infinity, there is a significant steady-state component of ICa ('window current') at plateau potentials in neonatal rat heart cells. Modulation of the steady-state and transient components of ICa by various agents can be attributed both to specific alterations in d infinity and f infinity and to more complicated alterations in the mode of calcium channel activity.

Full text

PDF
186

Selected References

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

  1. Attwell D., Cohen I., Eisner D., Ohba M., Ojeda C. The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Arch. 1979 Mar 16;379(2):137–142. doi: 10.1007/BF00586939. [DOI] [PubMed] [Google Scholar]
  2. Bean B. P. Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6388–6392. doi: 10.1073/pnas.81.20.6388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bezanilla F. A high capacity data recording device based on a digital audio processor and a video cassette recorder. Biophys J. 1985 Mar;47(3):437–441. doi: 10.1016/S0006-3495(85)83935-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown H. F., Kimura J., Noble D., Noble S. J., Taupignon A. The slow inward current, isi, in the rabbit sino-atrial node investigated by voltage clamp and computer simulation. Proc R Soc Lond B Biol Sci. 1984 Sep 22;222(1228):305–328. doi: 10.1098/rspb.1984.0066. [DOI] [PubMed] [Google Scholar]
  6. Byerly L., Hagiwara S. Calcium currents in internally perfused nerve cell bodies of Limnea stagnalis. J Physiol. 1982 Jan;322:503–528. doi: 10.1113/jphysiol.1982.sp014052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carbone E., Lux H. D. A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones. Nature. 1984 Aug 9;310(5977):501–502. doi: 10.1038/310501a0. [DOI] [PubMed] [Google Scholar]
  8. Cavalié A., Ochi R., Pelzer D., Trautwein W. Elementary currents through Ca2+ channels in guinea pig myocytes. Pflugers Arch. 1983 Sep;398(4):284–297. doi: 10.1007/BF00657238. [DOI] [PubMed] [Google Scholar]
  9. Colatsky T. J. Mechanisms of action of lidocaine and quinidine on action potential duration in rabbit cardiac Purkinje fibers. An effect on steady state sodium currents? Circ Res. 1982 Jan;50(1):17–27. doi: 10.1161/01.res.50.1.17. [DOI] [PubMed] [Google Scholar]
  10. Colquhoun D., Neher E., Reuter H., Stevens C. F. Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature. 1981 Dec 24;294(5843):752–754. doi: 10.1038/294752a0. [DOI] [PubMed] [Google Scholar]
  11. Fenwick E. M., Marty A., Neher E. Sodium and calcium channels in bovine chromaffin cells. J Physiol. 1982 Oct;331:599–635. doi: 10.1113/jphysiol.1982.sp014394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gadsby D. C., Kimura J., Noma A. Voltage dependence of Na/K pump current in isolated heart cells. Nature. 1985 May 2;315(6014):63–65. doi: 10.1038/315063a0. [DOI] [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. Hess P., Lansman J. B., Tsien R. W. Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells. J Gen Physiol. 1986 Sep;88(3):293–319. doi: 10.1085/jgp.88.3.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
  16. Hume J. R. Comparative interactions of organic Ca++ channel antagonists with myocardial Ca++ and K+ channels. J Pharmacol Exp Ther. 1985 Jul;234(1):134–140. [PubMed] [Google Scholar]
  17. 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]
  18. Josephson I. R., Sanchez-Chapula J., Brown A. M. A comparison of calcium currents in rat and guinea pig single ventricular cells. Circ Res. 1984 Feb;54(2):144–156. doi: 10.1161/01.res.54.2.144. [DOI] [PubMed] [Google Scholar]
  19. Kass R. S., Sanguinetti M. C. Inactivation of calcium channel current in the calf cardiac Purkinje fiber. Evidence for voltage- and calcium-mediated mechanisms. J Gen Physiol. 1984 Nov;84(5):705–726. doi: 10.1085/jgp.84.5.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kass R. S., Tsien R. W. Control of action potential duration by calcium ions in cardiac Purkinje fibers. J Gen Physiol. 1976 May;67(5):599–617. doi: 10.1085/jgp.67.5.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kass R. S., Tsien R. W. Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers. J Gen Physiol. 1975 Aug;66(2):169–192. doi: 10.1085/jgp.66.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kimura J., Noma A., Irisawa H. Na-Ca exchange current in mammalian heart cells. Nature. 1986 Feb 13;319(6054):596–597. doi: 10.1038/319596a0. [DOI] [PubMed] [Google Scholar]
  23. Langer G. A., Brady A. J., Tan S. T., Serena D. Correlation of the glycoside response, the force staircase, and the action potential configuration in the neonatal rat heart. Circ Res. 1975 Jun;36(6):744–752. doi: 10.1161/01.res.36.6.744. [DOI] [PubMed] [Google Scholar]
  24. Lee K. S., Marban E., Tsien R. W. Inactivation of calcium channels in mammalian heart cells: joint dependence on membrane potential and intracellular calcium. J Physiol. 1985 Jul;364:395–411. doi: 10.1113/jphysiol.1985.sp015752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lee K. S., Tsien R. W. High selectivity of calcium channels in single dialysed heart cells of the guinea-pig. J Physiol. 1984 Sep;354:253–272. doi: 10.1113/jphysiol.1984.sp015374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lee K. S., Tsien R. W. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983 Apr 28;302(5911):790–794. doi: 10.1038/302790a0. [DOI] [PubMed] [Google Scholar]
  27. Lee K. S., Tsien R. W. Reversal of current through calcium channels in dialysed single heart cells. Nature. 1982 Jun 10;297(5866):498–501. doi: 10.1038/297498a0. [DOI] [PubMed] [Google Scholar]
  28. McDonald T. F., Cavalié A., Trautwein W., Pelzer D. Voltage-dependent properties of macroscopic and elementary calcium channel currents in guinea pig ventricular myocytes. Pflugers Arch. 1986 May;406(5):437–448. doi: 10.1007/BF00583365. [DOI] [PubMed] [Google Scholar]
  29. McDonald T. F., Pelzer D., Trautwein W. Cat ventricular muscle treated with D600: characteristics of calcium channel block and unblock. J Physiol. 1984 Jul;352:217–241. doi: 10.1113/jphysiol.1984.sp015288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. McDonald T. F., Pelzer D., Trautwein W. On the mechanism of slow calcium channel block in heart. Pflugers Arch. 1980 May;385(2):175–179. doi: 10.1007/BF00588699. [DOI] [PubMed] [Google Scholar]
  31. Mitchell M. R., Powell T., Terrar D. A., Twist V. W. Characteristics of the second inward current in cells isolated from rat ventricular muscle. Proc R Soc Lond B Biol Sci. 1983 Oct 22;219(1217):447–469. doi: 10.1098/rspb.1983.0084. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Nilius B., Röder A. Direct evidence of a Ca-sensitive inactivation of slow inward channels in frog atrial myocardium. Biomed Biochim Acta. 1985;44(7-8):1151–1161. [PubMed] [Google Scholar]
  34. Nowycky M. C., Fox A. P., Tsien R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. doi: 10.1038/316440a0. [DOI] [PubMed] [Google Scholar]
  35. Reuter H., Stevens C. F., Tsien R. W., Yellen G. Properties of single calcium channels in cardiac cell culture. Nature. 1982 Jun 10;297(5866):501–504. doi: 10.1038/297501a0. [DOI] [PubMed] [Google Scholar]
  36. Sanguinetti M. C., Kass R. S. Regulation of cardiac calcium channel current and contractile activity by the dihydropyridine Bay K 8644 is voltage-dependent. J Mol Cell Cardiol. 1984 Jul;16(7):667–670. doi: 10.1016/s0022-2828(84)80631-8. [DOI] [PubMed] [Google Scholar]
  37. Sanguinetti M. C., Kass R. S. Voltage-dependent block of calcium channel current in the calf cardiac Purkinje fiber by dihydropyridine calcium channel antagonists. Circ Res. 1984 Sep;55(3):336–348. doi: 10.1161/01.res.55.3.336. [DOI] [PubMed] [Google Scholar]
  38. Sanguinetti M. C., Krafte D. S., Kass R. S. Voltage-dependent modulation of Ca channel current in heart cells by Bay K8644. J Gen Physiol. 1986 Sep;88(3):369–392. doi: 10.1085/jgp.88.3.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sheu S. S., Lederer W. J. Lidocaine's negative inotropic and antiarrhythmic actions. Dependence on shortening of action potential duration and reduction of intracellular sodium activity. Circ Res. 1985 Oct;57(4):578–590. doi: 10.1161/01.res.57.4.578. [DOI] [PubMed] [Google Scholar]
  40. Siegelbaum S. A., Tsien R. W. Calcium-activated transient outward current in calf cardiac Purkinje fibres. J Physiol. 1980 Feb;299:485–506. doi: 10.1113/jphysiol.1980.sp013138. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES