Articles |
From the Department of Physiology and the Medical Biotechnology Center (L.F.S., H.C., A.M.G., W.J.L.), University of Maryland at Baltimore School of Medicine, and the Department of Pharmacology and Clinical Pharmacology (M.B.C.), St George's Hospital Medical School, London, UK.
Abstract Ca2+ sparks, the elementary events underlying excitation-contraction (E-C) coupling, occur when sarcoplasmic reticulum (SR) Ca2+ release channels open. They are activated locally by Ca2+ influx through sarcolemmal (SL) Ca2+ channels. By measuring the probability of spark occurrence under conditions in which their probability of occurrence is low, we address two important questions raised by our recent work: (1) When a Ca2+ spark is triggered, how many SL Ca2+ channels (at a minimum) contribute to its activation? (2) What is the relation between the subcellular local [Ca2+]i produced by the opening of SL Ca2+ channels and the consequent SR Ca2+ release? By comparing the voltage dependence of Ca2+ sparks in rat ventricular myocytes with the Ca2+ current, we show that the opening of a single SL Ca2+ channel can trigger a Ca2+ spark. Furthermore, we deduce that the probability of SR Ca2+ release depends of the square of the local [Ca2+]i produced by SL Ca2+ channel openings. These results are discussed with respect to the properties of Ca2+-induced Ca2+ release (CICR) and the local control theory of excitation-contraction coupling.
Key Words: intracellular Ca2+ fluo 3 nifedipine Ca2+ current excitation-contraction coupling
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