Abstract
To study the effects of changes in sarcoplasmic reticulum (SR) intraluminal Ca2+ on the Ca2+ release mechanism, we correlated the activity of single cardiac ryanodine receptor (RyR) channels, monitored in planar bilayers, with the properties of spontaneous elementary Ca2+ release events (sparks) in intact ventricular myocytes, monitored by scanning confocal microfluorimetry. Under both normal conditions and Ca2+ overload, induced by elevation of extracellular [Ca2+], Ca2+ sparks represented single populations of events. During Ca2+ overload, the frequency of sparks increased from 0.8 to 3.1 events per second per 100 μm line scanned, and their amplitude increased from 100 nM to 400 nM. The duration of the Ca2+ sparks, however, was not altered. Changes in the properties of Ca2+ sparks were accompanied by only an ≈ 30% increase in the SR Ca2+ content, as determined by emptying the intracellular Ca2+ stores using caffeine. When single Ca2+ release channels were incorporated into lipid bilayers and activated by cytoplasmic Ca2+ (≈ 100 nM) and ATP (3 mM), elevation of Ca2+ on the luminal side from 20 μM to 0.2–20 mM resulted in a 1.2-fold to 7-fold increase, respectively, in open probability (P o). This potentiation of P o was due to an increase in mean open time and frequency of events. The relative effect of luminal Ca2+ was greater at low levels of cytoplasmic [Ca2+] than at high levels of cytoplasmic [Ca2+], and no effect of luminal Ca2+ was observed to occur in channels activated by 0.5–50 μM cytoplasmic Ca2+ in the absence of ATP. Our results suggest that SR Ca2+ release channels are modulated by SR intraluminal Ca2+. These alterations in properties of release channels may account for, or contribute to, the mechanism of spontaneous Ca2+ release in cardiac myocytes
Similar content being viewed by others
Reference
Ashley RH, Williams AJ (1990) Divalent cation activation and inhibition of single calcium release channels from sheep cardiac sarcoplasmic reticulum. J Gen Physiol 95: 981–1005
Bassani JWM, Yuan W, Bers DM (1995) Fractional SR Ca2+ release is regulated by trigger Ca2+ and SR Ca2+ content in cardiac myocytes. Am J Physiol 268: C1313-C1329
Bers DM (1991) Excitation-contraction coupling and contractile force. Kluwer Academic, Dordrecht
Cannell MB, Cheng H, Lederer WJ (1994) Spatial non-uniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes. Biophys J 67: 1942–1956
Cheng H, Cannell MB, Lederer WJ (1994) Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science 262: 740–744
Cheng H, Fill M, Valdivia HH, Lederer WJ (1995) Model of Ca2+ release channel adaptation. Science 267: 2000–2002
Cheng H, Lederer MR, Lederer WJ, Cannell MB (1996) Calcium sparks and [Ca2+]i waves in cardiac myocytes. Am J Physiol 270: C148-C159
Dettbarn C, Györke S, Palade P (1994) Many agonists induce “quantal” Ca2+ release or adaptive behavior in muscle ryanodine receptors. Mol Pharmacol 46: 502–507
Escobar AL, Cifuntes F, Vergara J (1995) Detection of Ca2+-transients elicited by flash photolysis of DM-nitrophen with a fast calcium indicator. FEBS Lett 364: 335–338
Fabiato A (1985) Time and calcium dependence of activation and inactivation of calcium-induced calcium release from the sarcoplasmic reticulum of a skinned canine cardiac purkinje cell. J Gen Physiol 85: 247–289
Fabiato A (1992) Two kinds of calcium-induced release of calcium from the sarcoplasmic reticulum of skinned cardiac cells. In: Frank GB (ed) Excitation-contraction coupling in skeletal, cardiac and smooth muscle. Plenum, New York, pp 245–262
Györke S, Fill M (1993) Ryanodine receptor adaptation: control mechanism of Ca2+-induced Ca2+ release in heart. Science 260: 807–809
Györke S, Palade P (1994) Ca2+-dependent negative control mechanism for Ca2+-induced Ca2+ release in crayfish muscle. J Physiol (Lond) 476: 315–322
Györke S, Velez P, Suarez-Isla B, Fill M (1994) Activation of single cardiac and skeletal ryanodine receptors by flash photolysis of caged Ca2+. Biophys J 66: 1879–1886
Han S, Schiefer A, Isenberg G (1994) Ca2+ load of guina-pig ventricular myocytes determines efficacy of brief Ca2+ currents as trigger for Ca2+ release. J Physiol (Lond) 480: 411–421
Janczewski AMJ, Spurgeon HA, Stern MD, Lakatta EG (1994) Effects of sarcoplasmic reticulum Ca2+ load on the gain function of Ca2+ release by Ca2+ current in cardiac cells. Am J Physiol 268: H916-H920
Meissner G (1994) Ryanodine receptor/Ca2+ release channels and their regulation by endogeneous effectors. Annu Rev Physiol 56: 485–508
Niggli E, Lipp P (1995) Subcellular features of calcium signaling in heart muscle: what do we learn. Cardiovasc Res 29: 441–448
Rosseau E, Meisner G (1989) Single cardiac sarcoplasmic reticulum Ca2+ release channel: activation by caffeine. Am J Physiol 256: H328-H333
Sitsapesan R, Williams AJ (1994) Regulation of the gating of the sheep cardiac sarcoplasmic reticulum Ca2+ release channel by luminal Ca2+. J Membr Biol 137: 215–226
Sitsapesan R, Williams AJ (1995) The gating of the sheep skeletal sarcoplasmic reticulum Ca2+-release channel is regulated by luminal Ca2+. J Membr Biol 146: 133–144
Stern MD (1992) Theory of excitation-contraction coupling in cardiac muscle. Biophys J 63: 495–517
Stern MD, Lakatta E (1992) Excitation-contraction in the heart: the state of the question. FASEB J 6: 3092–3100
Stern MD, Capogrossi MC, Lakatta EG (1988) Spontaneous calcium release from the sarcoplasmic reticulum in myocardial cells: mechanisms and consequences. Cell Calcium 9: 247–256
Tinker A, Lindsay ARG, Williams AJ (1993) Cation conduction in the calcium release channel of the cardiac sarcoplasmic reticulum under physiological and pathophysiological conditions. Cardiovasc Res 27: 1820–1825
Tu Q, Velez P, Cortez-Gutierrez M, Fill M (1994) Surface charge potentiates conduction through the cardiac ryanodine receptor channel. J Gen Physiol 103: 853–867
Volpe P, Simon BJ (1991) The bulk of Ca2+ released to the myoplasm is free in the sarcoplasmic reticulum and does not unbind from casequestrin. FEBS Lett. 278: 274–278
Yasui K, Palade P, Györke S (1994) Negative control mechanism with features of adaptation controls Ca2+ release in cardiac myocytes. Biophys J. 67: 457–460
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lukyanenko, V., Györke, I. & Györke, S. Regulation of calcium release by calcium inside the sarcoplasmic reticulum in ventricular myocytes. Pflügers Arch — Eur J Physiol 432, 1047–1054 (1996). https://doi.org/10.1007/s004240050233
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s004240050233