Effects of endothelin on the electrical activity of sino-atrial pacemaker cells of rabbit

The effects of endothelin-1 (ET-1) on the electrophysiological activity of pacemaker cells of rabbit sino-atrial node were examined by using intracellular microelectrode technique. The results obtained were as follows : (1) With superfusion of ET-1 (1-30 nmol/L), the velocity of diastolic depolarization (VDD) of pacemaker cells was significantly decreased in a concentration dependent manner, resulting in a reduced rate of pacemaker firing (RPF). (2) The decreases in RPF and VDD induced by ET-1 could be virtually blocked by pretreatment with ET(A) receptor blocker BQ-123 (20 or 100 μg/L). It was strongly suggested that the electrophysiological effects of ET-1 on the pacemaker cells were mediated by the ET(A) receptor. (3) The negative chronotropic action of ET-1 on the pacemaker cells was totally abolished by pretreatment with a kind of K(ATP) channel blocker glibenclamide (10 μmol/L). On the basis of above results, it appears that the binding of ET-1 with ET(A) receptor may induce an activation of K(ATP) channels with resultant increase in K⁺ current so as to decrease the velocity of diastolic depolarization in the pacemaker cells.