Satoh H
Department of Pharmacology, Nara Medical University, Japan.
J Cardiovasc Pharmacol. 1995 Jun;25(6):967-72. doi: 10.1097/00005344-199506000-00016.
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.
采用双微电极电压钳技术，研究了β-肾上腺素能受体阻断药（吲哚洛尔和普萘洛尔）对自发搏动的家兔窦房结细胞动作电位（AP）和膜电流的电生理效应。两种阻断药（10⁻⁷ - 10⁻⁶ M）累积给药均使动作电位时程（APD）延长，并呈浓度依赖性产生负性变时作用。普萘洛尔的反应比吲哚洛尔更强。在10⁻⁶ M时，普萘洛尔使最大舒张电位（MDP）去极化，吲哚洛尔显著降低最大去极化速率，但两种药物对动作电位幅度（APA）几乎没有影响或无影响。在电压钳实验中，两种阻断剂（10⁻⁷ - 10⁻⁶ M）均呈浓度依赖性抑制慢内向电流和时间依赖性外向电流。钳制电位为 - 40 mV。超极化激活内向电流不受吲哚洛尔影响，但被普萘洛尔浓度依赖性抑制。吲哚洛尔和普萘洛尔均未改变Isi的失活曲线。IK的激活曲线不受吲哚洛尔影响，但在10⁻⁶ M普萘洛尔作用下，在去极化方向上移位约11 mV。这些结果表明，两种β-肾上腺素能受体阻断药（吲哚洛尔和普萘洛尔）均抑制慢内向电流和时间依赖性外向电流，但由于它们的药理特性，对超极化激活内向电流和IK的激活动力学产生不同作用，从而导致家兔窦房结细胞自发活动降低存在差异。
