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) 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 (Vh) of -35 mV into and past the pacemaker-potential range resulted in a progressively larger i(f) associated with an increasing slope conductance. Cs+ (2 mM) reversibly blocked both i(f) and the slope conductance increase, suggesting that the current activated was indeed predominantly i(f). Subsequently, hyperpolarizing steps to -50, -60, and -70 mV were applied in the absence (to activate only i(f)) 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 i(f) 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 i(f) out of the pacemaker range (due to run-down) or an incomplete block of i(f). 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 i(f) 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).
Liu
Y M
YM
Department of Physiology and Biophysics, State University of New York, Health Science Center, Stony Brook 11794-8661, USA.
Yu
H
H
Li
C Z
CZ
Cohen
I S
IS
Vassalle
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002586:Cesium / Q000494:pharmacology*; D003971:Diastole / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology
D007473:Ion Channels; D002586:Cesium