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 iso lated 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 subs idiary pacemaker cells of the SA node, increasing [Cs](0) abolished di astolic depolarization (DD), but then (by depolarizing the cells to le ss negative potentials) Cs allowed the appearance of a shallow DD that maintained spontaneous discharge even in 20 mM Cs, In 10 mM [K](0), t he subsidiary pacemaker cells depolarized and exhibited action potenti als similar to those in dominant pacemaker cells. In high [K](0), the Na/K pump activity is stimulated: adding Cs initially increased the MD P minimally, but the subsequent decrease in MDP persisted. In preparat ions quiescent in high [K](0), Cs only depolarized the membrane and co uld induce spontaneous discharge: the action potentials were followed by an undershoot and DD, In high [K](0) plus norepinephrine, even 20 m M Cs did not suppress and might increase the rate of discharge. During quiescence in acetylcholine or carbachol (I-f is blocked), Cs still t ransiently hyperpolarized the resting potential. In zero [K](0) with o r without carbachol (I-f is absent or blocked), Cs hyperpolarized the quiescent membrane by stimulating the Na/K pump. Cs-induced hyperpolar ization was reduced by 50-100 mu M ouabain, We conclude that, in the S A node, dual pacemaker mechanisms are present in subsidiary cells, The pacemaker potential at more negative voltages is blocked by Cs, but t he dominant type pacemaker potential is not blocked even by 20 mM Cs ( which is known to completely block I-f). Cs initially hyperpolarizes a pparently by stimulating the Na/K pump (not by blocking I-f) and subse quently depolarizes the subsidiary pacemaker cells by blocking an outw ard current but not I-K1 (absent in the SA node). Thus, in the SA node I-f may play little role in pacemaker activity.