Signaling of Ca2+ release and contraction in cardiac myocytes.

Cross signaling between Ca2+ channel and ryanodine receptor was explored in whole cell clamped rat ventricular myocyte under conditions where global myoplasmic Ca2+ concentrations were strongly buffered by dialyzing the myocytes with high concentrations of Fura 2 and EGTA. Ca2+ channel and ryanodine receptor were respectively activated by a depolarizing pulse to -10 mV and rapid (< 50 ms) application of 5 mM caffeine. Temporal analysis of kinetics of inactivation of Ca2+ channel with respect to the time of application of caffeine pulse provided experimental evidence that signalling between the ryanodine and Ca2+ channel is mediated exclusively through the Ca2+ microdomains surrounding the DHP/ryanodine receptor complex independent of global myoplasmic Ca2+ concentrations.