Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1997 Aug 1;502(Pt 3):471–479. doi: 10.1111/j.1469-7793.1997.471bj.x

The effect of tetracaine on spontaneous Ca2+ release and sarcoplasmic reticulum calcium content in rat ventricular myocytes.

C L Overend 1, D A Eisner 1, S C O'Neill 1
PMCID: PMC1159521  PMID: 9279801

Abstract

1. The effects of tetracaine were studied on voltage-clamped rat ventricular myocytes, which exhibited Ca2+ overload as identified by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) as shown by the associated contractions. This Ca2+ release was initially abolished by tetracaine before returning at a lower frequency, but greater amplitude, than the control. On removal of tetracaine, there was a burst of spontaneous Ca2+ release activity. All these effects were dose dependent, from 25 to 200 microM tetracaine. 2. The spontaneous Ca2+ release activated an inward Na(+)-Ca2+ exchange current as Ca2+ was pumped out of the cell. The integral of this current (i.e. the Ca2+ efflux) was increased in the presence of tetracaine. The calcium efflux per unit time was unaffected by tetracaine. 3. The SR Ca2+ content was increased by tetracaine, as shown by the integral of the caffeine-evoked Na(+)-Ca2+ exchange current. The increase of SR Ca2+ content was equal to the extra Ca2+ lost from the cell during the burst on removal of tetracaine, and to estimates of the extra calcium gained over the quiescent period following addition of tetracaine. 4. It is concluded that partial inhibition of calcium-induced calcium release increases SR Ca2+ content. In the steady state, cell Ca2+ balance is maintained as the lower frequency of spontaneous release (that activates efflux) is compensated for by their greater size.

Full text

PDF
471

Selected References

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

  1. Bers D. M., Bridge J. H. Effect of acetylstrophanthidin on twitches, microscopic tension fluctuations and cooling contractures in rabbit ventricle. J Physiol. 1988 Oct;404:53–69. doi: 10.1113/jphysiol.1988.sp017278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carmeliet E., Morad M., Van der Heyden G., Vereecke J. Electrophysiological effects of tetracaine in single guinea-pig ventricular myocytes. J Physiol. 1986 Jul;376:143–161. doi: 10.1113/jphysiol.1986.sp016146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chamberlain B. K., Volpe P., Fleischer S. Inhibition of calcium-induced calcium release from purified cardiac sarcoplasmic reticulum vesicles. J Biol Chem. 1984 Jun 25;259(12):7547–7553. [PubMed] [Google Scholar]
  4. Cheng H., Lederer M. R., Lederer W. J., Cannell M. B. Calcium sparks and [Ca2+]i waves in cardiac myocytes. Am J Physiol. 1996 Jan;270(1 Pt 1):C148–C159. doi: 10.1152/ajpcell.1996.270.1.C148. [DOI] [PubMed] [Google Scholar]
  5. Cheng H., Lederer W. J., Cannell M. B. Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science. 1993 Oct 29;262(5134):740–744. doi: 10.1126/science.8235594. [DOI] [PubMed] [Google Scholar]
  6. Díaz M. E., Cook S. J., Chamunorwa J. P., Trafford A. W., Lancaster M. K., O'Neill S. C., Eisner D. A. Variability of spontaneous Ca2+ release between different rat ventricular myocytes is correlated with Na(+)-Ca2+ exchange and [Na+]i. Circ Res. 1996 May;78(5):857–862. doi: 10.1161/01.res.78.5.857. [DOI] [PubMed] [Google Scholar]
  7. Díaz M. E., Trafford A. W., O'Neill S. C., Eisner D. A. Measurement of sarcoplasmic reticulum Ca2+ content and sarcolemmal Ca2+ fluxes in isolated rat ventricular myocytes during spontaneous Ca2+ release. J Physiol. 1997 May 15;501(Pt 1):3–16. doi: 10.1111/j.1469-7793.1997.003bo.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eisner D. A., Lederer W. J., Sheu S. S. The role of intracellular sodium activity in the anti-arrhythmic action of local anaesthetics in sheep Purkinje fibres. J Physiol. 1983 Jul;340:239–257. doi: 10.1113/jphysiol.1983.sp014761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eisner D. A., Nichols C. G., O'Neill S. C., Smith G. L., Valdeolmillos M. The effects of metabolic inhibition on intracellular calcium and pH in isolated rat ventricular cells. J Physiol. 1989 Apr;411:393–418. doi: 10.1113/jphysiol.1989.sp017580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Györke S., Lukyanenko V., Györke I. Dual effects of tetracaine on spontaneous calcium release in rat ventricular myocytes. J Physiol. 1997 Apr 15;500(Pt 2):297–309. doi: 10.1113/jphysiol.1997.sp022021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Horn R., Marty A. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J Gen Physiol. 1988 Aug;92(2):145–159. doi: 10.1085/jgp.92.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kasai H., Petersen O. H. Spatial dynamics of second messengers: IP3 and cAMP as long-range and associative messengers. Trends Neurosci. 1994 Mar;17(3):95–101. doi: 10.1016/0166-2236(94)90112-0. [DOI] [PubMed] [Google Scholar]
  13. Komai H., Redon D., Rusy B. F. Procaine enhancement of the rapid cooling contracture and inhibition of the decay of potentiated state in rabbit papillary muscle. J Mol Cell Cardiol. 1995 Dec;27(12):2543–2550. doi: 10.1006/jmcc.1995.0041. [DOI] [PubMed] [Google Scholar]
  14. Lederer W. J., Tsien R. W. Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J Physiol. 1976 Dec;263(2):73–100. doi: 10.1113/jphysiol.1976.sp011622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Negretti N., Varro A., Eisner D. A. Estimate of net calcium fluxes and sarcoplasmic reticulum calcium content during systole in rat ventricular myocytes. J Physiol. 1995 Aug 1;486(Pt 3):581–591. doi: 10.1113/jphysiol.1995.sp020836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Petersen C. C., Toescu E. C., Petersen O. H. Different patterns of receptor-activated cytoplasmic Ca2+ oscillations in single pancreatic acinar cells: dependence on receptor type, agonist concentration and intracellular Ca2+ buffering. EMBO J. 1991 Mar;10(3):527–533. doi: 10.1002/j.1460-2075.1991.tb07979.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Satoh H., Delbridge L. M., Blatter L. A., Bers D. M. Surface:volume relationship in cardiac myocytes studied with confocal microscopy and membrane capacitance measurements: species-dependence and developmental effects. Biophys J. 1996 Mar;70(3):1494–1504. doi: 10.1016/S0006-3495(96)79711-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tinker A., Williams A. J. Charged local anesthetics block ionic conduction in the sheep cardiac sarcoplasmic reticulum calcium release channel. Biophys J. 1993 Aug;65(2):852–864. doi: 10.1016/S0006-3495(93)81104-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Varro A., Negretti N., Hester S. B., Eisner D. A. An estimate of the calcium content of the sarcoplasmic reticulum in rat ventricular myocytes. Pflugers Arch. 1993 Apr;423(1-2):158–160. doi: 10.1007/BF00374975. [DOI] [PubMed] [Google Scholar]
  20. Volpe P., Palade P., Costello B., Mitchell R. D., Fleischer S. Spontaneous calcium release from sarcoplasmic reticulum. Effect of local anesthetics. J Biol Chem. 1983 Oct 25;258(20):12434–12442. [PubMed] [Google Scholar]
  21. Xu L., Jones R., Meissner G. Effects of local anesthetics on single channel behavior of skeletal muscle calcium release channel. J Gen Physiol. 1993 Feb;101(2):207–233. doi: 10.1085/jgp.101.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zahradníková A., Palade P. Procaine effects on single sarcoplasmic reticulum Ca2+ release channels. Biophys J. 1993 Apr;64(4):991–1003. doi: 10.1016/S0006-3495(93)81465-6. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES