Sarcoplasmic reticulum Ca release in intact ventricular myocytes

Sarcoplasmic reticulum (SR) Ca release in intact ventricular myocytes is the major source of Ca which activates cardiac contraction (although Ca influx makes a non-negligible contribution in most species). The fundamental events of SR Ca release are known as Ca sparks. The twitch Ca transient is composed of approximately 10,000 Ca sparks occurring in a given cell, and they are synchronized by the action potential and Ca current. Many factors influence SR Ca release amplitude and kinetics, and the focus here is on understanding how these factors work in the intact cellular environment. The intracellular Ca (Cai) and intra-SR Ca (CaSR) are two of the most important dynamic modulators of SR Ca release. Indeed, while Cai (and Ca current which initiates systolic SR Ca release) is widely acknowledged to be important, it is increasingly clear that CaSR changes dynamically under physiological conditions and that this has very important regulatory effects on the SR Ca release process. While elevation of CaSR obviously increases the driving force and amount of SR Ca available for release, it also increases the fractional release and can be responsible for spontaneous diastolic SR Ca release. These issues are discussed in both normal physiological and pathophysiological contexts.