Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1994 Nov 1;480(Pt 3):411–421. doi: 10.1113/jphysiol.1994.sp020371

Ca2+ load of guinea-pig ventricular myocytes determines efficacy of brief Ca2+ currents as trigger for Ca2+ release.

S Han 1, A Schiefer 1, G Isenberg 1
PMCID: PMC1155816  PMID: 7869256

Abstract

1. In guinea-pig ventricular cells, the concentration of ionized cytosolic calcium ([Ca2+]o) was estimated from the fluorescence of 100 microM K5-indo-1. At 36 degrees C and 2 mM [Ca2+]o, the Ca2+ load of the cells was varied by 1 Hz trains of conditioning clamp pulses to -30 mV (low Ca2+ load), 0 mV (intermediate Ca2+ load) and paired pulses (high Ca2+ load). After seven pulses potentiation was steady and short test pulses to 0 mV were tested for their efficacy in triggering [Ca2+]c transients. The influx of trigger Ca2+ was graded by varying the test-pulse duration between 1 and 180 ms. 2. After a 3 min rest period, [Ca2+]c was 100 +/- 20 nM (mean +/- S.E.M.) and 2 ms test pulses were unable to induce [Ca2+]c transients. Test pulses of 2 ms duration, however, induced [Ca2+]c transients after potentiation with single or paired pulses. 3. At high cellular Ca2+ load, the amplitude of the [Ca2+]c transients (delta[Ca2+]c) gradually increased with pulse durations up to 8 ms. Pulse durations between 8 and 160 ms, however, did not further increase delta[Ca2+]c as if the largest part of the [Ca2+]c transient was due to regenerative contribution of Ca(2+)-induced Ca2+ release. 4. Pulses of 160 ms duration induced 'saturating' responses whose amplitudes delta[Ca2+]c, t = infinity decreased from 938 +/- 120 nM at high Ca2+ load, to 610 +/- 90 and 350 +/- 120 nM at intermediate and low Ca2+ loads, respectively. 5. Delta[Ca2+]c was more sensitive to the duration of Ca2+ influx at low or intermediate Ca2+ loads than at high Ca2+ load. When delta[Ca2+]c was plotted against the test-pulse duration, 50% of delta[Ca2+]c, t = infinity was found to be at 9 +/- 2 ms (low), 4.6 +/- 1 ms (intermediate) or 1.8 +/- 0.5 ms pulses (high Ca2+ load). Correspondingly, the efficacy of 2 ms test pulses in triggering [Ca2+]c transients increased with the Ca2+ load. 6. At high Ca2+ load, [Ca2+]c peaked nearly independently of pulse duration at 19 +/- 3 ms. At intermediate or low Ca2+ load, time to peak increased with pulse duration. 7. The results confirm the theory that sarcoplasmic reticulum (SR) Ca2+ release contributes an amount to the [Ca2+]c transient that increases with the cellular Ca2+ load. The results are compatible with the hypothesis that SR Ca2+ release can be activated by both Ca2+ influx and by SR Ca2+ release and that the latter mechanism constitutes a positive feedback, the amplification of which increases with the amount of releasable Ca2+.

Full text

PDF
414

Selected References

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

  1. Ashley R. H., Williams A. J. Divalent cation activation and inhibition of single calcium release channels from sheep cardiac sarcoplasmic reticulum. J Gen Physiol. 1990 May;95(5):981–1005. doi: 10.1085/jgp.95.5.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bers D. M., Lederer W. J., Berlin J. R. Intracellular Ca transients in rat cardiac myocytes: role of Na-Ca exchange in excitation-contraction coupling. Am J Physiol. 1990 May;258(5 Pt 1):C944–C954. doi: 10.1152/ajpcell.1990.258.5.C944. [DOI] [PubMed] [Google Scholar]
  3. Beuckelmann D. J., Wier W. G. Mechanism of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells. J Physiol. 1988 Nov;405:233–255. doi: 10.1113/jphysiol.1988.sp017331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beuckelmann D. J., Wier W. G. Sodium-calcium exchange in guinea-pig cardiac cells: exchange current and changes in intracellular Ca2+. J Physiol. 1989 Jul;414:499–520. doi: 10.1113/jphysiol.1989.sp017700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cannell M. B., Berlin J. R., Lederer W. J. Effect of membrane potential changes on the calcium transient in single rat cardiac muscle cells. Science. 1987 Dec 4;238(4832):1419–1423. doi: 10.1126/science.2446391. [DOI] [PubMed] [Google Scholar]
  6. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol. 1983 Jul;245(1):C1–14. doi: 10.1152/ajpcell.1983.245.1.C1. [DOI] [PubMed] [Google Scholar]
  7. Fabiato A. Myoplasmic free calcium concentration reached during the twitch of an intact isolated cardiac cell and during calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned cardiac cell from the adult rat or rabbit ventricle. J Gen Physiol. 1981 Nov;78(5):457–497. doi: 10.1085/jgp.78.5.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fabiato A. Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol. 1985 Feb;85(2):291–320. doi: 10.1085/jgp.85.2.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ganitkevich V Y. a., Isenberg G. Depolarization-mediated intracellular calcium transients in isolated smooth muscle cells of guinea-pig urinary bladder. J Physiol. 1991 Apr;435:187–205. doi: 10.1113/jphysiol.1991.sp018505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  11. Hansford R. G., Lakatta E. G. Ryanodine releases calcium from sarcoplasmic reticulum in calcium-tolerant rat cardiac myocytes. J Physiol. 1987 Sep;390:453–467. doi: 10.1113/jphysiol.1987.sp016711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hilgemann D. W., Collins A., Matsuoka S. Steady-state and dynamic properties of cardiac sodium-calcium exchange. Secondary modulation by cytoplasmic calcium and ATP. J Gen Physiol. 1992 Dec;100(6):933–961. doi: 10.1085/jgp.100.6.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Isenberg G., Han S. Gradation of Ca(2+)-induced Ca2+ release by voltage-clamp pulse duration in potentiated guinea-pig ventricular myocytes. J Physiol. 1994 Nov 1;480(Pt 3):423–438. doi: 10.1113/jphysiol.1994.sp020372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Isenberg G., Wendt-Gallitelli M. F. Binding of calcium to myoplasmic buffers contributes to the frequency-dependent inotropy in heart ventricular cells. Basic Res Cardiol. 1992 Sep-Oct;87(5):411–417. doi: 10.1007/BF00795053. [DOI] [PubMed] [Google Scholar]
  16. Janczewski A. M., Lewartowski B. The effect of prolonged rest on calcium exchange and contractions in rat and guinea-pig ventricular myocardium. J Mol Cell Cardiol. 1986 Dec;18(12):1233–1242. doi: 10.1016/s0022-2828(86)80427-8. [DOI] [PubMed] [Google Scholar]
  17. Leblanc N., Hume J. R. Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum. Science. 1990 Apr 20;248(4953):372–376. doi: 10.1126/science.2158146. [DOI] [PubMed] [Google Scholar]
  18. Lee H. C., Clusin W. T. Cytosolic calcium staircase in cultured myocardial cells. Circ Res. 1987 Dec;61(6):934–939. doi: 10.1161/01.res.61.6.934. [DOI] [PubMed] [Google Scholar]
  19. Stern M. D. Theory of excitation-contraction coupling in cardiac muscle. Biophys J. 1992 Aug;63(2):497–517. doi: 10.1016/S0006-3495(92)81615-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wendt-Gallitelli M. F. Ca-pools involved in the regulation of cardiac contraction under positive inotropy. X-ray microanalysis on rapidly-frozen ventricular muscles of guinea-pig. Basic Res Cardiol. 1986;81 (Suppl 1):25–32. doi: 10.1007/978-3-662-11374-5_3. [DOI] [PubMed] [Google Scholar]
  21. Wendt-Gallitelli M. F., Isenberg G. Total and free myoplasmic calcium during a contraction cycle: x-ray microanalysis in guinea-pig ventricular myocytes. J Physiol. 1991 Apr;435:349–372. doi: 10.1113/jphysiol.1991.sp018514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wendt-Gallitelli M. F., Isenberg G. X-ray microanalysis of single cardiac myocytes frozen under voltage-clamp conditions. Am J Physiol. 1989 Feb;256(2 Pt 2):H574–H583. doi: 10.1152/ajpheart.1989.256.2.H574. [DOI] [PubMed] [Google Scholar]
  23. Wier W. G., Egan T. M., López-López J. R., Balke C. W. Local control of excitation-contraction coupling in rat heart cells. J Physiol. 1994 Feb 1;474(3):463–471. doi: 10.1113/jphysiol.1994.sp020037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. duBell W. H., Houser S. R. Voltage and beat dependence of Ca2+ transient in feline ventricular myocytes. Am J Physiol. 1989 Sep;257(3 Pt 2):H746–H759. doi: 10.1152/ajpheart.1989.257.3.H746. [DOI] [PubMed] [Google Scholar]

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

RESOURCES