Effects of ketanserin on the pacemaker activity of rabbit sinus node in vitro.

Electrophysiological effects of ketanserin on pacemaker activity of rabbit sinus node cells were studied using double-microelectrode voltage clamp method. Ketanserin (10(-5) mol/l) caused an increase in spontaneous cycle length accompanied by decreases in the maximum upstroke velocity of the action potential, the slope of the phase 4 depolarization and the action potential amplitude. On the current systems, ketanserin reduced the slow inward current (Isi) and the time-dependent potassium outward current (IK) in a dose-dependent manner. As for a decrease in the outward current, the agent did not change the steady-state activation of IK. These observations indicate that ketanserin does not have a specific effect on a single current system, but that the drug exerts an inhibitory effect on the electrical activity of the sinus node pacemaker cells.