Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Jun;84(11):3941–3945. doi: 10.1073/pnas.84.11.3941

Potentiation of the calcium-channel currents of internally perfused mammalian heart cells by repetitive depolarization.

K S Lee
PMCID: PMC304992  PMID: 2438689

Abstract

The Ca2+ current of single ventricular cells perfused internally by the suction-pipette method can be increased ("potentiated") progressively with repeated stimulation. In Na+- and K+-free external solution containing Ca+, the potentiation response begins to appear at a step potential to -20 mV from a holding potential of -90 mV, reaching a maximum at 0-10 mV. Thus, maximal potentiation coincides with peak inward Ca2+ current. The time course of potentiation development and decline is very slow, occurring in seconds; the former is voltage-dependent, whereas the latter is not. Concomitant with the peak current increase, current decay during the pulse is slowed markedly, thus resulting in the persistence of significant Ca2+ influx at the end of the pulse. With nonperfused single cells, a similar stimulation protocol elicits a similar increase in cell contractility. It is concluded that the Ca2+ channel, after being opened by a single step depolarization, can be opened further by repeating the same step at an appropriate frequency. This additional channel opening is likely to be responsible for the generation of the positive force "staircase" of the myocardial cells in response to increased heart rate.

Full text

PDF
3941

Selected References

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

  1. Aldrich R. W., Jr, Getting P. A., Thompson S. H. Mechanism of frequency-dependent broadening of molluscan neurone soma spikes. J Physiol. 1979 Jun;291:531–544. doi: 10.1113/jphysiol.1979.sp012829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Eckert R., Lux H. D. Calcium-dependent depression of a late outward current in snail neurons. Science. 1977 Jul 29;197(4302):472–475. doi: 10.1126/science.17921. [DOI] [PubMed] [Google Scholar]
  4. Eckert R., Tillotson D. L., Brehm P. Calcium-mediated control of Ca and K currents. Fed Proc. 1981 Jun;40(8):2226–2232. [PubMed] [Google Scholar]
  5. Eckert R., Tillotson D., Ridgway E. B. Voltage-dependent facilitation of Ca2+ entry in voltage-clamped, aequorin-injected molluscan neurons. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1748–1752. doi: 10.1073/pnas.74.4.1748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Gibbons W. R., Fozzard H. A. Slow inward current and contraction of sheep cardiac Purkinje fibers. J Gen Physiol. 1975 Mar;65(3):367–384. doi: 10.1085/jgp.65.3.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hagiwara S., Byerly L. Calcium channel. Annu Rev Neurosci. 1981;4:69–125. doi: 10.1146/annurev.ne.04.030181.000441. [DOI] [PubMed] [Google Scholar]
  9. Heyer C. B., Lux H. D. Properties of a facilitating calcium current in pace-maker neurones of the snail, Helix pomatia. J Physiol. 1976 Nov;262(2):319–348. doi: 10.1113/jphysiol.1976.sp011598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoshi T., Rothlein J., Smith S. J. Facilitation of Ca2+-channel currents in bovine adrenal chromaffin cells. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5871–5875. doi: 10.1073/pnas.81.18.5871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lee K. S., Akaike N., Brown A. M. The suction pipette method for internal perfusion and voltage clamp of small excitable cells. J Neurosci Methods. 1980 Feb;2(1):51–78. doi: 10.1016/0165-0270(80)90045-x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Lee K. S., Noble D., Lee E., Spindler A. J. A new calcium current underlying the plateau of the cardiac action potential. Proc R Soc Lond B Biol Sci. 1984 Nov 22;223(1230):35–48. doi: 10.1098/rspb.1984.0081. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. 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]
  17. Noble S., Shimoni Y. The calcium and frequency dependence of the slow inward current 'staircase' in frog atrium. J Physiol. 1981 Jan;310:57–75. doi: 10.1113/jphysiol.1981.sp013537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Noble S., Shimoni Y. Voltage-dependent potentiation of the slow inward current in frog atrium. J Physiol. 1981 Jan;310:77–95. doi: 10.1113/jphysiol.1981.sp013538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983 Feb 17;301(5901):569–574. doi: 10.1038/301569a0. [DOI] [PubMed] [Google Scholar]
  20. Tillotson D., Horn R. Inactivation without facilitation of calcium conductance in caesium-loaded neurones of Aplysia. Nature. 1978 May 25;273(5660):312–314. doi: 10.1038/273312a0. [DOI] [PubMed] [Google Scholar]
  21. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES