Alternans-possible mechanisms for generating it by modification of intracellular Ca++ 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⁺⁺ flow and concentrations in a myocyte, specifically those related to the sarcoplasmic reticulum (SR). The model includes regulation of the membrane SR Ca⁺⁺ channels kinetics by changes in free [Ca⁺⁺] near the openings of Ca⁺⁺ channels, by a combination of positive and negative central loops. The model predicts changes of cytoplasmatic and SR [Ca ⁺⁺], 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⁺⁺ 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⁺⁺ release channels, which may produce instabilities-e.g. alternans