Alternans - Possible Mechanisms for Generating it by Modification of Intracellular Ca~(++) Availability

摘要

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 control 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.