What determines the initiation of the heartbeat?

The origin of the heartbeat in the sino-atrial (SA) node is usually thought to arise from the sequential activation of a variety of ionic currents in pacemaker cells (Irisawa et al. 1993). Recently, the possibility has been considered that heart rate might be influenced by transient changes in cytosolic Ca2+. Rubenstein & Lipsius (1989) demonstrated that in cat subsidiary pacemaker cells the late phase of diastolic depolarization was slowed in the presence of ryanodine to selectively inhibit Ca2+ release from the sarcoplasmic reticulum (SR). Primary pacemaker cells also have a SR-dependence of cardiac pacemaking since the rate of beating of guinea-pig SA node/atrial preparations was slowed in the presence of either ryanodine or cyclopiazonic acid (an inhibitor of the SR Ca2+-ATPase). The reduction in rate was associated with changes in action potential characteristics recorded intracellularly (Rigg & Terrar, 1996). The role of Ca2+ release from the SR in influencing pacemaker rate appears to be a common mechanism in many types of pacemaking tissue since the rate reducing effects of ryanodine have been observed in other mammalian cells (rabbit SA, e.g. Hata et al. 1996; and atrioventricular node, Hancox et al. 1994) and in amphibian pacemaker cells (Ju & Allen, 1998).