Cesium effects on if and iK 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) node 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). However, 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 range of potentials were studied in the same single SA node cell at the same time by means of the perforated patch-clamp technique. Hyperpolarizing steps from a holding potential (V-h) Of -35 mV into and past the pacemaker-potential range resulted in a progressively larger if associated with an increasing slope conductance. Cs+ (2 mM) reversibly blocked both if and the slope conductance increase, suggesting that the current activated was indeed predominantly if. Subsequently, hyperpolarizing steps to -50, -60, and -70 mV were applied in the absence (to activate only if) and in the presence of a prior depolarizing step to +10 mV (to activate i(K) as well, as the action potential normally does). Cs+ almost abolished if but only slightly decreased i(K). It is concluded 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-down) or an incomplete block of if. Instead, the resistance of i(K) to block by Cs+ is consistent with a predominant role of i(K) for the discharge of the SA node, although if can contribute under normal or special circumstances. The reduction of i(K) by Cs+ raises the question whether the Cs+ slows the SA-node discharge not only by suppressing I-f, but also by reducing i(K).