Intracellular Ca(2+) concentration and rate adaptation of the cardiac action potential.

Influx of Ca(2+) ions through the cardiac plasma membrane contributes to the shaping of the action potential plateau and acts as trigger for the release of Ca(2+) ions from the sarcoplasmic reticulum and the initiation of the contractile process. The increased intracellular Ca(2+) concentration feeds back on the channels and transporters in the plasma membrane and modulates the electrical activity. This interaction and its change with rate of pacing is the topic of this review, which is subdivided in three parts. In part I a description is given of different channels and transporters that carry Ca(2+) ions, or are activated-modulated by intracellular Ca(2+) ions. In part II an analysis is given of the changes in action potential duration and shape when stimuli are applied in the relative refractory period (electrical restitution) and when rate is suddenly increased and kept at the higher level until steady-state is obtained. A description of experimental findings in each case is followed by a discussion of possible mechanisms. Part III deals with physiopathological aspects of Ca(2+) handling and discusses recent information on hypertrophy, heart failure and atrial fibrillation.