Spontaneous electrical activity of guinea-pig sinoatrial cells under modulation of two different pacemaker mechanisms

The main cellular determinants of cardiac automaticity are the hyperpolarization-activated cationic current If, and the electrogenic Na+/Ca2+ exchanger which generates an inward current after each action potential (AP). Our goal was to evaluate their relative role in pacemaking, by means of application of Ivabradine (IVA) (specific If blocker) and Ryanodine (RYA) (known to abolish calcium transient) on enzimatically isolated guinea-pig pacemaker cells. Spontaneous APs were recorded in patch-clamp whole cell configuration at 36°C from 7 cells perfused with the following sequence of solutions: physiological normal tyrode (NT), IVA 3 mM, NT and RYA 3 mM. Cycle length (CL, ms) and diastolic depolarization rate (DDR, V/s) were also calculated. Both blockers displayed similar effects, increasing CL (by 27 and 30%, respectively), and decreasing DDR (by 34 and 42%) with respect to NT exposure. These results suggest that both mechanisms are involved into pacemaking mechanism at a similar degree.