CESIUM EFFECTS ON I(F) AND I(K) IN RABBIT SINOATRIAL NODE MYOCYTES - IMPLICATIONS FOR SA NODE AUTOMATICITY

Cesium blocks the hyperpolarization-activated current i(f) but blocks neither the delayed-rectifier current i(K) nor the sinoatrial (SA) nod e discharge. It has been proposed that the failure of Cs+ to block SA discharge is either an incomplete block or a negative shift of i(f). H owever, an alternative possibility is that i(K) (rather than i(f)) has a predominant role in the SA-pacemaker potential. To investigate this point, the effects of Cs+ on both i(f) and i(K) in the pacemaker rang e of potentials were studied in the same single SA node cell at the sa me time by means of the perforated patch-clamp technique. Hyperpolariz ing steps from a holding potential (V-h) Of -35 mV into and past the p acemaker-potential range resulted in a progressively larger if associa ted with an increasing slope conductance. Cs+ (2 mM) reversibly blocke d both if and the slope conductance increase, suggesting that the curr ent activated was indeed predominantly if. Subsequently, hyperpolarizi ng steps to -50, -60, and -70 mV were applied in the absence (to activ ate only if) and in the presence of a prior depolarizing step to +10 m V (to activate i(K) as well, as the action potential normally does). C s+ almost abolished if but only slightly decreased i(K). It is conclud ed that the failure of Cs+ to block the SA- node spontaneous discharge is not due to a shift of if out of the pacemaker range (due to run-do wn) or an incomplete block of if. Instead, the resistance of i(K) to b lock by Cs+ is consistent with a predominant role of i(K) for the disc harge of the SA node, although if can contribute under normal or speci al circumstances. The reduction of i(K) by Cs+ raises the question whe ther the Cs+ slows the SA-node discharge not only by suppressing I-f, but also by reducing i(K).