Spontaneous beating of guinea pig sinoatrial cells under pharmacological modulation of two different pacemaker mechanisms.

Two main mechanisms, one related to If current and the other to the intracellular calcium cycling, are proposed to underlie the diastolic depolarization (DD) phase of the action potential of sinoatrial cells (SANCs). The relative contribution of the two mechanisms is still unclear, and their regulation is of great clinical and pharmacological interest. The aim of our study was to compare the effect of 3μM Ivabradine (IVA, specific If blocker) and of the same concentration of Ryanodine (RYA, blocker, at this concentration, of sarcoplamic calcium release channels) on action potential (AP) parameters of guinea-pig SANCs, via the patch-clamp whole cell technique. Analogous studies have been previously performed on other mammalian species. Series of APs were recorded from spontaneously beating cells, under perfusion in physiological Normal Tyrode (NT) solution at 36°C, until a steady-state (SS) AP waveform was reached; perfusion solution was then rapidly switched to IVA, and APs recorded until a new SS (3 to 5 minutes), then again to NT. The protocol was then repeated with RYA. On 7 cells, both blockers displayed, with respect to NT, comparable effects on AP parameters. In particular, they increased beating cycle length (by 27 and 30% respectively), and decreased the DD rate (by 34 and 42%). These results suggest, among other things, that each mechanism can ensure maintenance of pacemaking, in case of pathological or pharmacological downregulation of the other one.