Control of the pacemaker activity of the sinoatrial node by intracellular Ca2+. Experiments and modelling

The possible effects of intracellular Ca2+ on the pacemaker of the heart, t he sinoatrial node, are reviewed. In mammalian sinoatrial node, reduction o r abolition of the intracellular Ca2+ transient by ryanodine, sarcoplasmic reticulum Ca2+ pump block or 1,2-bis(2.-aminophenoxy)ethane-N,N,N ' ,N ' -t etraacetic acid (BAPTA) reduces the spontaneous rate by 21-32%, whereas in amphibian sinus venosus it abolishes spontaneous activity. In rabbit sinoat rial node, ryanodine/BAPTA reduces the T-type Ca2+ current (i(Ca,T)), perha ps slows inactivation of the L-type Ca2+ current (i(Ca,L)), reduces the inw ard Na+-Ca2+ exchange current (i(NaCa)), and reduces the rapid and slow del ayed rectifier K+ currents (i(K,r) and i(K,s), respectively). Other evidenc e shows that a reduction of intracellular Ca inhibits the hyperpolarization -activated current (i(f)). These putative intracellular Ca2+-dependent chan ges in ionic currents have been incorporated into different models of rabbi t sinoatrial node action potentials. In the models, block of the Ca2+ trans ient reduced the spontaneous rate by 24 and 26% in the central and peripher al models of Zhang and others, 13% in the Oxsoft model (Noble et al.), 9% i n the model of Wilders and others, and 41% in the model of Demir and others . In all models, the reduction in rate was not primarily the result of the decrease in i(NaCa), but instead the combination of all changes in ionic cu rrents.