Termination of Ca2+ release during Ca2+ sparks in rat ventricular myocytes

1 Confocal Ca2+ imaging was used to measure spontaneous release events (Ca2+ sparks) in fluo‐3‐loaded isolated rat ventricular myocytes. 2 The microscopic Ca2+ release flux underlying Ca2+ sparks was derived by adapting the methods used previously to describe macroscopic Ca2+ release from cell‐averaged Ca2+ transients. 3 The magnitude of the local release fluxes varied from 2 to 5 μM ms−1, depending on SR Ca2+ loading conditions. Following spontaneous activation, the release flux rapidly decayed (τ= 6–12 ms). The rate of termination of release flux was found to be directly related to the magnitude of the flux (r2= 0.88). 4 The rate of termination of local release flux was slowed in the presence of FK506, a compound that is known to reduce inactivation of SR Ca2+ channels in vitro. 5 These results suggest that termination of release flux during sparks is not due to a spontaneous stochastic decay process or local depletion of Ca2+ from the SR, but rather involves an active extinguishing mechanism such as Ca2+‐dependent inactivation or adaptation.

[1]  D M Bers,et al.  Passive Ca buffering and SR Ca uptake in permeabilized rabbit ventricular myocytes. , 1993, The American journal of physiology.

[2]  W. Wier,et al.  Flux of Ca2+ across the sarcoplasmic reticulum of guinea‐pig cardiac cells during excitation‐contraction coupling. , 1991, The Journal of physiology.

[3]  S. Györke,et al.  Role of local Ca2+ domains in activation of Ca(2+)-induced Ca2+ release in crayfish muscle fibers. , 1993, The American journal of physiology.

[4]  W. Lederer,et al.  Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. , 1993, Science.

[5]  E. Lakatta,et al.  The immunophilin FK506‐binding protein modulates Ca2+ release channel closure in rat heart. , 1997, The Journal of physiology.

[6]  E. Ríos,et al.  A general procedure for determining the rate of calcium release from the sarcoplasmic reticulum in skeletal muscle fibers. , 1987, Biophysical journal.

[7]  S. Baylor,et al.  Resting myoplasmic free calcium in frog skeletal muscle fibers estimated with fluo-3. , 1993, Biophysical journal.

[8]  H G Othmer,et al.  A model of calcium dynamics in cardiac myocytes based on the kinetics of ryanodine-sensitive calcium channels. , 1994, Biophysical journal.

[9]  I. Györke,et al.  Dual effects of tetracaine on spontaneous calcium release in rat ventricular myocytes. , 1997, The Journal of physiology.

[10]  P. Lipp,et al.  Submicroscopic calcium signals as fundamental events of excitation‐‐contraction coupling in guinea‐pig cardiac myocytes. , 1996, The Journal of physiology.

[11]  L. Blatter,et al.  Sarcoplasmic reticulum Ca2+ release flux underlying Ca2+ sparks in cardiac muscle. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[12]  E. Lakatta,et al.  Excitation‐contraction coupling in the heart: the state of the question 1 , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  S. Györke,et al.  Negative control mechanism with features of adaptation controls Ca2+ release in cardiac myocytes. , 1994, Biophysical journal.

[14]  D. Bers,et al.  Effects of FK-506 on contraction and Ca2+ transients in rat cardiac myocytes. , 1996, Circulation research.

[15]  L. Rosenhead.  Conduction of Heat in Solids , 1947, Nature.

[16]  A. Fabiato,et al.  Time and calcium dependence of activation and inactivation of calcium- induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell , 1985, The Journal of general physiology.

[17]  A. Escobar,et al.  Detection of Ca2+‐transients elicited by flash photolysis of DM‐nitrophen with a fast calcium indicator , 1995, FEBS letters.

[18]  F. Protasi,et al.  Formation and maturation of the calcium release apparatus in developing and adult avian myocardium. , 1996, Developmental biology.

[19]  W. Wier,et al.  Mechanism of release of calcium from sarcoplasmic reticulum of guinea‐pig cardiac cells. , 1988, The Journal of physiology.

[20]  M. Stern,et al.  Theory of excitation-contraction coupling in cardiac muscle. , 1992, Biophysical journal.

[21]  G. Langer,et al.  Calcium concentration and movement in the diadic cleft space of the cardiac ventricular cell. , 1996, Biophysical journal.

[22]  W. Lederer,et al.  Effect of membrane potential changes on the calcium transient in single rat cardiac muscle cells. , 1987, Science.

[23]  A. Fabiato.  Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell , 1985, The Journal of general physiology.

[24]  P. Lipp,et al.  Modulation of Ca2+ release in cultured neonatal rat cardiac myocytes. Insight from subcellular release patterns revealed by confocal microscopy. , 1994, Circulation research.

[25]  S. Györke,et al.  Ryanodine receptor adaptation: control mechanism of Ca(2+)-induced Ca2+ release in heart. , 1993, Science.