Clinical Electrophysiology of the Calcium Antagonists

In the century since calcium was shown to be essential in the normal function of the myocardium (1) little further information on the importance was available until Fleckenstein and colleagues (2) proposed the concept of calcium antagonism. A variety of substances were shown to be capable of inhibiting the transmembrane passage of calcium ions. Although this work had concentrated on the role of calcium in the myocardium the profound influence of these compounds was evident in the cells of the specialised conducting system. It has become apparent that the transmembrane flux of calcium is a fundamental but complex procedure: additionally this calcium transfer subserves different purposes in different types of cells. In the myocardium calcium is of fundamental importance in excitation-contraction coupling but of limited importance is electrical depolarisation. The contrast, calcium is of profound importance in the generation and propagation of electrical activity in the SA and AV nodes. Although, in both the transitional cells of the SA node and the N cells of the AV node, sodium ions have a role in the initial generation of the action potential it is calcium which determines to a greater extent the upstroke velocity and the speed of repolarisation. Thus substances which impair the transmembrane movement of calcium ions may have electrophysiological actions throughout the action potential. Translating these influences from the single cell to the intact heart would suggest that an influence on the upstroke velocity of the action potential will slow conduction while a prolongation of repolarisation will lengthen the refractory period and slow the slope of spontaneous distolic depolarisation. Where calcium antagonists have clinical electrophysiological actions these are the fundamental effects although our ability to observe changing SA nodal function in man is very limited.