Different actions between pindolol and propranolol on the ionic currents in spontaneously beating rabbit sino-atrial...

Electrophysiological effects of beta-adrenoceptor blocking drugs (pindolol and propranolol) on the action potentials (APs) and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined by the two-microelectrode voltage-clamp technique. Cumulative administrations of both blocking drugs (10(-7)-10(-6) M) prolonged the AP duration (APD) and caused a negative chronotropic effect in a concentration-dependent manner. Propranolol exhibited stronger responses than pindolol. At 10(-6) M, propranolol depolarized the maximum diastolic potential (MDP) and pindolol decreased the maximum rate of depolarization significantly, but the drugs had little or no effect on the AP amplitude (APA). In voltage-clamp experiments, both blockers (10(-7)-10(-6) M) inhibited the slow inward and the time-dependent outward currents in a concentration-dependent manner. Holding potential was -40 mV. The hyperpolarization-activated inward current was not affected by pindolol, but it was concentration-dependently inhibited by propranolol. The inactivation curve of Isi was not modified by either pindolol or propranolol. The activation curve of IK was unaffected by pindolol, but was shifted by propranolol 10(-6) M by approximately 11 mV in the depolarizing direction. These results indicate that both beta-adrenoceptor blocking drugs (pindolol and propranolol) inhibit the slow inward and the time-dependent outward currents, but produce different actions on the hyperpolarization-activated inward current and the activation kinetic of IK due to their pharmacological properties, thereby resulting in difference in decrease in the spontaneous activity of rabbit SA node cells.