Electrophysiological study of alinidine in voltage clamped rabbit sino-atrial node cells

Abstract

Electrophysiological effects of alinidine on rabbit sino-atrial node cells were examined. Alinidine was applied in concentrations between 0.3 and 100 μg/ml and decreased the spontaneous frequency in a dose-dependent manner. The maximum rate of rise and the amplitude of action potentials of the spontaneously beating rabbit sino-atrial node were decreased in the presence of alinidine concentrations higher than 10 and 100 μg/ml, respectively. The maximum diastolic potential was depolarized by alinidine at 100 μg/ml. The main effect of alinidine was a dose-dependent decrease in slope of diastolic depolarization (a prolongation of the cycle length) and a delayed repolarization of the action potential. In voltage clamp experiments, alinidine suppressed the slow inward current (I s) and the outward current (I k) dose dependently, without altering steady-state inactivation of I s (f ∞) and the activation of I k (p ∞). The hyperpolarization-activated inward current (I h) was also reduced. These results suggested that alinidine decreased I s, I k and I h due to reduction in the conductance of these current systems. The changes in the ionic currents in the presence of alinidine can explain the changes in configuration of the action potential and must contribute to the negative chronotropic action of alinidine.