Excitation-contraction coupling was studied in mammalian cardiac cells in which the opening probability of L-type calcium (Ca2 +) channels was reduced. Confocal microscopy during voltage-clamp depolarization revealed distinct local transients inthe concentration of intracellular calcium ions ([Ca2 +]¡). When voltage was varied, the latency to occurrence and the relative probability of occurrence of local [Ca2 +]; transients varied as predicted if ca2 + release from the sarcoplasmic reticulum (SR) was linked tightly to Ca2 + flux through L-type Ca2 + channels but not to that through the Na-Ca exchanger or to average [Ca2 +];. Voltage had no effect on the amplitude of local [Ca2 +]; transients. Thus, the most efficacious "Ca2 + signal" for activating Ca2 + release from the SR may be a transient microdomain of high [Ca2 +]; beneath an individual, open L-type Ca2 + channel
