NON-MUSCARINIC AND NON-NICOTINIC INHIBITION BY THE ACETYLCHOLINE ANALOGUE CARBACHOL OF THE DELAYED RECTIFIER POTASSIUM CURRENT, i_K, IN RABBIT ISOLATED SINO-ATRIAL NODE CELLS

Abstract

The effect of carbachol, an analogue of acetylcholine, on the delayed rectifier potassium current, i_K, was investigated in rabbit isolated sino-atrial node cells using the whole cell patch clamp technique with amphotericin-permeabilized patches. In the presence of 500 nM atropine and 500 nM hexamethonium to block muscarinic and nicotinic receptors, respectively, 500 nM carbachol decreased the amplitude and rate of deactivation of i_K without, however, affecting the slope of the i_K activation curve. The same concentration of carbachol decreased the pacemaking rate of spontaneously active sino-atrial node cells by more than 13 %. Thus, there is a non-muscarinic and non-nicotinic pathway for cholinergically induced reduction in the amplitude and rate of deactivation of i_K that would appear to contribute to negative chronotropy in rabbit sino-atrial node pacemaker cells.