Alternans-possible mechanisms for generating it by modification of intracellular Ca/sup ++/ availability

This study describes a cellular mechanism responsible for causing mechanical and electrical alternans. It is based on a model of the regulating mechanisms of Ca/sup ++/ flow and concentrations in a myocyte, specifically those related to the sarcoplasmic reticulum (SR). The model includes regulation of the membrane SR Ca/sup ++/ channels kinetics by changes in free [Ca/sup ++/] near the openings of Ca/sup ++/ channels, by a combination of positive and negative central loops. The model predicts changes of cytoplasmatic and SR [Ca/sup ++/], including dependence on the beat intervals, either constant or during premature and delayed beats. Non-linear dependence is described between the degree of recovery of the release mechanism and the amount of Ca/sup ++/ released from the SR. This dependence is sufficient to produce mechanical and electrical alternans. The results support the basic hypothesis of control of the SR Ca/sup ++/ release channels, which may produce instabilities-e.g. alternans.