Cesium effects on dual pacemaker mechanisms in guinea pig sinoatrial node

The aim of the present experiments was to study the effects of cesium (Cs) on dual pacemaker potentials and the underlying mechanisms in isolated sinoatrial (SA) node of the guinea pig superfused in vitro. Cs (1-20 mM) initially hyperpolarized the maximum diastolic potential (MDP) and then depolarized it in a concentration-dependent manner. In subsidiary pacemaker cells of the SA node, increasing [Cs]o abolished diastolic depolarization (DD), but then (by depolarizing the cells to less negative potentials) Cs allowed the appearance of a shallow DD that maintained spontaneous discharge even in 20 mM Cs. In 10 mM [K]o, the subsidiary pacemaker cells depolarized and exhibited action potentials similar to those in dominant pacemaker cells. In high [K]o, the Na/K pump activity is stimulated: adding Cs initially increased the MDP minimally, but the subsequent decrease in MDP persisted. In preparations quiescent in high [K]o, Cs only depolarized the membrane and could induce spontaneous discharge: the action potentials were followed by an undershoot and DD. In high [K]o plus norepinephrine, even 20 mM Cs did not suppress and might increase the rate of discharge. During quiescence in acetylcholine or carbachol (I(f) is blocked), Cs still transiently hyperpolarized the resting potential. In zero [K]o with or without carbachol (I(f) is absent or blocked), Cs hyperpolarized the quiescent membrane by stimulating the Na/K pump. Cs-induced hyperpolarization was reduced by 50-100 microM ouabain. We conclude that, in the SA node, dual pacemaker mechanisms are present in subsidiary cells. The pacemaker potential at more negative voltages is blocked by Cs, but the dominant type pacemaker potential is not blocked even by 20 mM Cs (which is known to completely block I(f). Cs initially hyperpolarizes apparently by stimulating the Na/K pump (not by blocking I(f)) and subsequently depolarizes the subsidiary pacemaker cells by blocking an outward current but not IK1 (absent in the SA node). Thus, in the SA node I(f) may play little role in pacemaker activity.