Inhibition by Compound II, a sotalol analogue, of delayed rectifier current (iK) in rabbit isolated sino-atrial node cells

The effects of Compound II, a sotalol analogue, on spontaneous electrical activity and on three membrane currents (the delayed rectifier current, iK, the long-lasting inward calcium current, iCa,L and hyperpolarization activated inward current, if) were investigated in rabbit isolated sino-atrial node cells by whole cell clamp with amphotericin-permeabilised patches. A submaximal concentration of Compound II (50 nM) had a significant effect on the time and voltage dependent activation of iK and caused a positive shift of the iK activation curve. As well as blocking iKr, it caused some degree of block of iKs. Block of iK by Compound II was found to be concentration dependent with an IC50 of approximately 40 nM. 1 μM Compound II nearly completely blocked iK without significantly affecting the peak current or I/V relationships of iCa,L or if. 50 nM Compound II caused a significant prolongation of APD100 and of cycle length. It also decreased diastolic depolarization rate without significantly affecting MDP and action 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 iK.