Intracellular Ca2+ concentration and rate adaptation of the cardiac action potential

Influx of Ca2+ ions through the cardiac plasma membrane contributes to the shaping of the action potential plateau and acts as trigger for the release of Ca2+ ions from the sarcoplasmic reticulum and the initiation of the contractile process. The increased intracellular Ca2+ 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 Ca2+ ions, or are activated-modulated by intracellular Ca2+ 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 Ca2+ handling and discusses recent information on hypertrophy, heart failure and atrial fibrillation. (C) 2004 Elsevier Ltd. All rights reserved.