Rosen M R, Weiss R M, Danilo P
J Pharmacol Exp Ther. 1984 Dec;231(3):566-71.
Previous studies have shown that alpha adrenergic stimulation can reduce the automaticity of canine Purkinje fibers. In the present study, our interest was to determine whether this is an alpha-1 or alpha-2 adrenergic action. We used standard microelectrode techniques to study the effects of the alpha agonists, phenylephrine and clonidine, and the alpha antagonists, prazosin and yohimbine, on phenylephrine-induced decreases in automaticity. Prazosin and yohimbine, 1 X 10(-5) M, alone, significantly reduced the amplitude and upstroke velocity (Vmax) of stimulated action potentials. In addition, yohimbine, 1 X 10(-5) M, accelerated and prazosin, 1 X 10(-5) M, attenuated repolarization. Prazosin, 1 X 10(-5) M, and yohimbine greater than or equal to 1 X 10(-7) M, alone, decreased automaticity. Phenylephrine, 5 X 10(-8) M, alone, significantly increased the cycle length of automatic Purkinje fibers. The effects of phenylephrine on automaticity were blocked by prazosin but not by yohimbine. Clonidine, alone, 1 X 10(-6) and 1 X 10(-5) M, significantly reduced automaticity, an effect that was not blocked by yohimbine or prazosin. Clonidine, 1 X 10(-6) and 1 X 10(-5) M, also significantly reduced Vmax and prolonged action potential duration of driven Purkinje fibers, an action consistent with direct membrane effects. These experiments suggest that the negative chronotropic effects of phenylephrine on Purkinje fiber automaticity are mediated by alpha-1 adrenergic receptors.
以往的研究表明，α肾上腺素能刺激可降低犬浦肯野纤维的自律性。在本研究中，我们感兴趣的是确定这是α1还是α2肾上腺素能作用。我们使用标准微电极技术研究了α激动剂去氧肾上腺素和可乐定以及α拮抗剂哌唑嗪和育亨宾对去氧肾上腺素引起的自律性降低的影响。单独使用1×10⁻⁵M的哌唑嗪和育亨宾可显著降低刺激动作电位的幅度和上升速度（Vmax）。此外，1×10⁻⁵M的育亨宾可加速复极化，而1×10⁻⁵M的哌唑嗪则使其衰减。单独使用1×10⁻⁵M的哌唑嗪和大于或等于1×10⁻⁷M的育亨宾可降低自律性。单独使用5×10⁻⁸M的去氧肾上腺素可显著增加自律性浦肯野纤维的周期长度。去氧肾上腺素对自律性的影响被哌唑嗪阻断，但未被育亨宾阻断。单独使用1×10⁻⁶M和1×10⁻⁵M的可乐定可显著降低自律性，这一作用未被育亨宾或哌唑嗪阻断。1×10⁻⁶M和1×10⁻⁵M的可乐定还可显著降低驱动浦肯野纤维的Vmax并延长动作电位持续时间，这一作用与直接膜效应一致。这些实验表明，去氧肾上腺素对浦肯野纤维自律性的负性变时作用是由α1肾上腺素能受体介导的。
