Class III Antiarrhythmic Drugs (amiodarone, Bretylium and Sotalol) on Action Potentials and Membrane Currents in Rabbit Sino-atrial Node Preparations

Electrophysiological effects of class III antiarrhythmic drugs (amiodarone, bretylium and sotalol) were examined in spontaneously beating and voltage-clamped rabbit sino-atrial node preparations, using a two microelectrode technique. At 10(-6) mol/l these class III antiarrhythmic drugs prolonged the cycle length significantly, but did not affect the action potential duration. At high concentration (10(-4) mol/l), amiodarone and sotalol prolonged the action potential duration as well as the cycle length. Sotalol 10(-5) mol/l depolarized the maximum diastolic potential. Amiodarone 10(-4) mol/l and bretylium 10(-5) mol/l depressed the maximum rate of depolarization. At concentrations ranging from 10(-7) to 10(-4) mol/l, amiodarone induced dysrhythmia in 5 of 10 preparations and bretylium in 3 of 7 preparations, but sotalol in none of 5 preparations. In voltage-clamped sino-atrial node preparations, all the class III antiarrhythmic drugs decreased the slow inward current in a concentration-dependent manner. The steady-state outward and the hyperpolarization-activated inward currents were also reduced. Sotalol (10(-5) mol/l) decreased both the outward current and the hyperpolarization-activated inward current stronger than the slow inward current. In addition, amiodarone (3 x 10(-6) mol/l) depressed the inactivation curve for the slow inward current, but it did not shift the potential of half-maximum inactivation. The drugs also depressed the activation curve for the outward current in a concentration-dependent manner. However, the values of half-maximum activations were not influenced by these drugs as compared to control.(ABSTRACT TRUNCATED AT 250 WORDS)