Effect of propafenone on the membrane currents of rabbit sino-atrial node cells

The effects of propafenone (1-50 micrograms/ml) on the membrane potential and currents of the rabbit sino-atrial node were studied using the voltage clamp technique. Propafenone decreased the heart rate, amplitude of the action potential and maximum rate of depolarization. It also depolarized the maximum diastolic potential and the resting potential and prolonged the action potential duration dose dependently. On the current systems of the sino-atrial node, propafenone reduced the outward current (ik), the inward current activated by hyperpolarization (ih) and the slow inward current (is) dose dependently. The decrease in is and ik by propafenone was due to the reductions in their conductance, not to the changes in the voltage dependence of the inactivation of is or activation of ik. The decrease in ik might be the ionic mechanism of the negative chronotropic effect of propafenone.