Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1997 Nov 1;504(Pt 3):565–578. doi: 10.1111/j.1469-7793.1997.565bd.x

Calcium-induced release of strontium ions from the sarcoplasmic reticulum of rat cardiac ventricular myocytes.

C I Spencer 1, J R Berlin 1
PMCID: PMC1159961  PMID: 9401965

Abstract

1. The effects of strontium ions, Sr2+, on Ca(2+)-dependent feedback mechanisms during excitation-contraction coupling were examined in voltage-clamped rat ventricular myocytes in which intracellular [Ca2+] and [Sr2+] were monitored with the fluorescent indicator, indo-1. 2. Voltage clamp depolarizations and caffeine applications during superfusion in Ca(2+)-free, Sr(2+)-containing solutions were employed to exchange intracellular Ca2+ with Sr2+. Myocytes were loaded with Sr2+ by applying voltage clamp depolarizations during superfusion in Na(+)-free, Sr(2+)-containing solutions. 3. Caffeine applications produced large fluorescence transients in Sr(2+)-loaded cells. Thus, Sr2+ could be sequestered and released from the sarcoplasmic reticulum. 4. Ca2+ influx, but not Sr2+ influx, via sarcolemmal Ca2+ channels evoked ryanodine-sensitive fluorescence transients in Sr(2+)-loaded cells. These results demonstrated that Ca2+ influx-induced Sr2+ release (CISR) from the sarcoplasmic reticulum occurred in these experiments, even though Sr2+ influx-induced Sr2+ release was not observed. 5. The amplitude of the Ca2+ influx-induced fluorescence transient was 17 +/- 1% of the caffeine-induced transient (n = 5 cells), an indication that fractional utilization of Sr2+ sequestered in the sarcoplasmic reticulum during CISR was low. 6. With increased Sr2+ loading, the amplitude of Ca2+ influx- and caffeine-induced fluorescence transients increased, but fractional utilization of sarcoplasmic reticulum divalent cation stores was independent of the degree of Sr2+ loading. These data suggest that Ca2+ influx directly activated the release of divalent cations from the sarcoplasmic reticulum, but mechanisms promoting positive feedback of Sr2+ release were minimal during CISR. 7. By comparison, in Ca(2+)-loaded myocytes, Ca2+ influx-induced Ca2+ release (CICR) utilized a greater fraction of caffeine-releasable stores than CISR. Fractional utilization of Ca2+ stores during CICR increased with the degree of Ca2+ loading. 8. Taken together, these results suggest that Ca(2+)-dependent feedback mechanisms play a major role in determining the extent of sarcoplasmic reticulum Ca2+ release during cardiac excitation-contraction coupling under a wide range of conditions.

Full text

PDF
565

Selected References

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

  1. Babu A., Scordilis S. P., Sonnenblick E. H., Gulati J. The control of myocardial contraction with skeletal fast muscle troponin C. J Biol Chem. 1987 Apr 25;262(12):5815–5822. [PubMed] [Google Scholar]
  2. Bassani J. W., Yuan W., Bers D. M. Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes. Am J Physiol. 1995 May;268(5 Pt 1):C1313–C1319. doi: 10.1152/ajpcell.1995.268.5.C1313. [DOI] [PubMed] [Google Scholar]
  3. Berlin J. R., Bassani J. W., Bers D. M. Intrinsic cytosolic calcium buffering properties of single rat cardiac myocytes. Biophys J. 1994 Oct;67(4):1775–1787. doi: 10.1016/S0006-3495(94)80652-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berlin J. R., Cannell M. B., Lederer W. J. Cellular origins of the transient inward current in cardiac myocytes. Role of fluctuations and waves of elevated intracellular calcium. Circ Res. 1989 Jul;65(1):115–126. doi: 10.1161/01.res.65.1.115. [DOI] [PubMed] [Google Scholar]
  5. Berlin J. R., Konishi M. Ca2+ transients in cardiac myocytes measured with high and low affinity Ca2+ indicators. Biophys J. 1993 Oct;65(4):1632–1647. doi: 10.1016/S0006-3495(93)81211-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berman M. C., King S. B. Stoichiometries of calcium and strontium transport coupled to ATP and acetyl phosphate hydrolysis by skeletal sarcoplasmic reticulum. Biochim Biophys Acta. 1990 Nov 16;1029(2):235–240. doi: 10.1016/0005-2736(90)90159-l. [DOI] [PubMed] [Google Scholar]
  7. Bers D. M., Berlin J. R. Kinetics of [Ca]i decline in cardiac myocytes depend on peak [Ca]i. Am J Physiol. 1995 Jan;268(1 Pt 1):C271–C277. doi: 10.1152/ajpcell.1995.268.1.C271. [DOI] [PubMed] [Google Scholar]
  8. Borzak S., Kelly R. A., Krämer B. K., Matoba Y., Marsh J. D., Reers M. In situ calibration of fura-2 and BCECF fluorescence in adult rat ventricular myocytes. Am J Physiol. 1990 Sep;259(3 Pt 2):H973–H981. doi: 10.1152/ajpheart.1990.259.3.H973. [DOI] [PubMed] [Google Scholar]
  9. Cannell M. B., Cheng H., Lederer W. J. Spatial non-uniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes. Biophys J. 1994 Nov;67(5):1942–1956. doi: 10.1016/S0006-3495(94)80677-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cannell M. B., Cheng H., Lederer W. J. The control of calcium release in heart muscle. Science. 1995 May 19;268(5213):1045–1049. doi: 10.1126/science.7754384. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Cheng H., Lederer M. R., Xiao R. P., Gómez A. M., Zhou Y. Y., Ziman B., Spurgeon H., Lakatta E. G., Lederer W. J. Excitation-contraction coupling in heart: new insights from Ca2+ sparks. Cell Calcium. 1996 Aug;20(2):129–140. doi: 10.1016/s0143-4160(96)90102-5. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Donoso P., Prieto H., Hidalgo C. Luminal calcium regulates calcium release in triads isolated from frog and rabbit skeletal muscle. Biophys J. 1995 Feb;68(2):507–515. doi: 10.1016/S0006-3495(95)80212-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Fabiato A. Rapid ionic modifications during the aequorin-detected calcium transient in a skinned canine cardiac Purkinje cell. J Gen Physiol. 1985 Feb;85(2):189–246. doi: 10.1085/jgp.85.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Grégoire G., Loirand G., Pacaud P. Ca2+ and Sr2+ entry induced Ca2+ release from the intracellular Ca2+ store in smooth muscle cells of rat portal vein. J Physiol. 1993 Dec;472:483–500. doi: 10.1113/jphysiol.1993.sp019957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Han S., Schiefer A., Isenberg G. Ca2+ load of guinea-pig ventricular myocytes determines efficacy of brief Ca2+ currents as trigger for Ca2+ release. J Physiol. 1994 Nov 1;480(Pt 3):411–421. doi: 10.1113/jphysiol.1994.sp020371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Herrmann-Frank A., Lehmann-Horn F. Regulation of the purified Ca2+ release channel/ryanodine receptor complex of skeletal muscle sarcoplasmic reticulum by luminal calcium. Pflugers Arch. 1996 May;432(1):155–157. doi: 10.1007/s004240050117. [DOI] [PubMed] [Google Scholar]
  21. Horiuti K. Some properties of the contractile system and sarcoplasmic reticulum of skinned slow fibres from Xenopus muscle. J Physiol. 1986 Apr;373:1–23. doi: 10.1113/jphysiol.1986.sp016032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ikemoto N., Ronjat M., Mészáros L. G., Koshita M. Postulated role of calsequestrin in the regulation of calcium release from sarcoplasmic reticulum. Biochemistry. 1989 Aug 8;28(16):6764–6771. doi: 10.1021/bi00442a033. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Janczewski A. M., Spurgeon H. A., Stern M. D., Lakatta E. G. Effects of sarcoplasmic reticulum Ca2+ load on the gain function of Ca2+ release by Ca2+ current in cardiac cells. Am J Physiol. 1995 Feb;268(2 Pt 2):H916–H920. doi: 10.1152/ajpheart.1995.268.2.H916. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Kawai M., Konishi M. Measurement of sarcoplasmic reticulum calcium content in skinned mammalian cardiac muscle. Cell Calcium. 1994 Aug;16(2):123–136. doi: 10.1016/0143-4160(94)90007-8. [DOI] [PubMed] [Google Scholar]
  27. Kimura J., Miyamae S., Noma A. Identification of sodium-calcium exchange current in single ventricular cells of guinea-pig. J Physiol. 1987 Mar;384:199–222. doi: 10.1113/jphysiol.1987.sp016450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. King B. W., Bose D. Mechanism of biphasic contractions in strontium-treated ventricular muscle. Circ Res. 1983 Jan;52(1):65–75. doi: 10.1161/01.res.52.1.65. [DOI] [PubMed] [Google Scholar]
  29. Konishi M., Berlin J. R. Ca transients in cardiac myocytes measured with a low affinity fluorescent indicator, furaptra. Biophys J. 1993 Apr;64(4):1331–1343. doi: 10.1016/S0006-3495(93)81494-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lipp P., Niggli E. Microscopic spiral waves reveal positive feedback in subcellular calcium signaling. Biophys J. 1993 Dec;65(6):2272–2276. doi: 10.1016/S0006-3495(93)81316-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lipp P., Niggli E. Submicroscopic calcium signals as fundamental events of excitation--contraction coupling in guinea-pig cardiac myocytes. J Physiol. 1996 Apr 1;492(Pt 1):31–38. doi: 10.1113/jphysiol.1996.sp021286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lukyanenko V., Györke I., Györke S. Regulation of calcium release by calcium inside the sarcoplasmic reticulum in ventricular myocytes. Pflugers Arch. 1996 Oct;432(6):1047–1054. doi: 10.1007/s004240050233. [DOI] [PubMed] [Google Scholar]
  33. López-López J. R., Shacklock P. S., Balke C. W., Wier W. G. Local calcium transients triggered by single L-type calcium channel currents in cardiac cells. Science. 1995 May 19;268(5213):1042–1045. doi: 10.1126/science.7754383. [DOI] [PubMed] [Google Scholar]
  34. López-López J. R., Shacklock P. S., Balke C. W., Wier W. G. Local, stochastic release of Ca2+ in voltage-clamped rat heart cells: visualization with confocal microscopy. J Physiol. 1994 Oct 1;480(Pt 1):21–29. doi: 10.1113/jphysiol.1994.sp020337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Mitra R., Morad M. A uniform enzymatic method for dissociation of myocytes from hearts and stomachs of vertebrates. Am J Physiol. 1985 Nov;249(5 Pt 2):H1056–H1060. doi: 10.1152/ajpheart.1985.249.5.H1056. [DOI] [PubMed] [Google Scholar]
  37. Niggli E. Strontium-induced creep currents associated with tonic contractions in cardiac myocytes isolated from guinea-pigs. J Physiol. 1989 Jul;414:549–568. doi: 10.1113/jphysiol.1989.sp017703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. O'Neill S. C., Mill J. G., Eisner D. A. Local activation of contraction in isolated rat ventricular myocytes. Am J Physiol. 1990 Jun;258(6 Pt 1):C1165–C1168. doi: 10.1152/ajpcell.1990.258.6.C1165. [DOI] [PubMed] [Google Scholar]
  39. Sipido K. R., Wier W. G. Flux of Ca2+ across the sarcoplasmic reticulum of guinea-pig cardiac cells during excitation-contraction coupling. J Physiol. 1991 Apr;435:605–630. doi: 10.1113/jphysiol.1991.sp018528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sitsapesan R., Williams A. J. Regulation of the gating of the sheep cardiac sarcoplasmic reticulum Ca(2+)-release channel by luminal Ca2+. J Membr Biol. 1994 Feb;137(3):215–226. doi: 10.1007/BF00232590. [DOI] [PubMed] [Google Scholar]
  41. Spencer C. I., Berlin J. R. Control of sarcoplasmic reticulum calcium release during calcium loading in isolated rat ventricular myocytes. J Physiol. 1995 Oct 15;488(Pt 2):267–279. doi: 10.1113/jphysiol.1995.sp020965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Takamatsu T., Wier W. G. Calcium waves in mammalian heart: quantification of origin, magnitude, waveform, and velocity. FASEB J. 1990 Mar;4(5):1519–1525. doi: 10.1096/fasebj.4.5.2307330. [DOI] [PubMed] [Google Scholar]
  44. Trafford A. W., Lipp P., O'Neill S. C., Niggli E., Eisner D. A. Propagating calcium waves initiated by local caffeine application in rat ventricular myocytes. J Physiol. 1995 Dec 1;489(Pt 2):319–326. doi: 10.1113/jphysiol.1995.sp021053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tripathy A., Meissner G. Sarcoplasmic reticulum lumenal Ca2+ has access to cytosolic activation and inactivation sites of skeletal muscle Ca2+ release channel. Biophys J. 1996 Jun;70(6):2600–2615. doi: 10.1016/S0006-3495(96)79831-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wier W. G., Cannell M. B., Berlin J. R., Marban E., Lederer W. J. Cellular and subcellular heterogeneity of [Ca2+]i in single heart cells revealed by fura-2. Science. 1987 Jan 16;235(4786):325–328. doi: 10.1126/science.3798114. [DOI] [PubMed] [Google Scholar]
  47. Winegrad S. Intracellular calcium binding and release in frog heart. J Gen Physiol. 1973 Dec;62(6):693–706. doi: 10.1085/jgp.62.6.693. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES