INHIBITION BY COMPOUND-II, A SOTALOL ANALOG, OF DELAYED RECTIFIER CURRENT (I(K)) IN RABBIT ISOLATED SINOATRIAL NODE CELLS

The effects of Compound II, a sotalol analogue, on spontaneous electri cal activity and on three membrane currents (the delayed rectifier cur rent, i(K), the long-lasting inward calcium current, i(Ca,L) and hyper polarization activated inward current, i(f)) were investigated in rabb it isolated sino-atrial node cells by whole cell clamp with amphoteric in-permeabilised patches. A submaximal concentration of Compound Il (5 0 nM) had a significant effect on the time and voltage dependent activ ation of i(K) and caused a positive shift of the i(K) activation curve . As well as blocking i(Kr), it caused some degree of block of i(Ks). Block of i(K) by Compound II was found to be concentration dependent w ith an IC50 of approximately 40 nM. 1 mu M Compound n nearly completel y blocked i(K) without significantly affecting the peak current or I/V relationships of i(Ca,L) or i(f). 50 nM Compound II caused a signific ant prolongation of APD(100) and of cycle length. It also decreased di astolic depolarization rate without significantly affecting MDP and ac tion potential amplitude. It is concluded that Compound II, a sotalol analogue, slows spontaneous activity of isolated rabbit SA node cells through a selective inhibition of i(K).