Ferrier G R, Carmeliet E
Laboratory of Physiology, University of Leuven, Belgium.
J Mol Cell Cardiol. 1990 Feb;22(2):191-200. doi: 10.1016/0022-2828(90)91115-n.
Reported effects of alpha-adrenergic agents on oscillatory afterpotentials (OAP) are conflicting. Therefore, we used standard two microelectrode voltage clamp techniques to determine the effects of phenylephrine and prazosin on the transient inward current (Iti) responsible for OAP. The Iti was induced in isolated rabbit Purkinje fibers either by acetylstrophanthidin or 8 mM Ca. The magnitude of the Iti was determined at various membrane potentials after activation by steps to -10 mV from a holding potential of -80 mV. When the Iti was induced by acetylstrophanthidin, phenylephrine (10(-7) to 10(-5)M) caused inhibition of Iti at all potentials tested. Phenylephrine also caused a significant decrease in net outward current at plateau voltages. Both effects were blocked by prazosin (5 x 10(-7)M) but not by propranolol (5 x 10(-7)M). Prazosin also strongly inhibited the Iti in the absence of phenylephrine. At 5 x 10(-7)M, prazosin did not affect sodium current activated by voltage steps from -80 to -45 mV or maximum upstroke velocity during interruptions of the voltage clamp. When the Iti was induced by 8 mM Ca, the effect of phenylephrine, but not prazosin, reversed so that phenylephrine increased the amplitude of the Iti. Thus, alpha-adrenergic agonists may exert either inhibitory or stimulatory effects on the Iti depending on the mechanism by which the current is induced. Additional effects on OAP amplitude may be induced by changes in action potential duration mediated through actions on net outward current. Prazosin may suppress OAP by an action on the Iti which is independent of alpha-adrenergic or local anaesthetic actions.
关于α-肾上腺素能药物对振荡后电位（OAP）的作用报道相互矛盾。因此，我们使用标准的双微电极电压钳技术来确定去氧肾上腺素和哌唑嗪对负责OAP的瞬时内向电流（Iti）的影响。在分离的兔浦肯野纤维中，通过毒毛花苷或8 mM钙诱导产生Iti。在从-80 mV的 holding 电位跃升至-10 mV激活后，在不同膜电位下测定Iti的幅度。当通过毒毛花苷诱导产生Iti时，去氧肾上腺素（10^(-7)至10^(-5)M）在所有测试电位下均导致Iti受到抑制。去氧肾上腺素还使平台电压下的净外向电流显著降低。这两种作用均被哌唑嗪（5×10^(-7)M）阻断，但未被普萘洛尔（5×10^(-7)M）阻断。在没有去氧肾上腺素的情况下，哌唑嗪也强烈抑制Iti。在5×10^(-7)M时，哌唑嗪不影响从-80 mV至-45 mV电压阶跃激活的钠电流或电压钳中断期间的最大除极速度。当通过8 mM钙诱导产生Iti时，去氧肾上腺素的作用发生逆转，但哌唑嗪的作用未逆转，因此去氧肾上腺素增加了Iti的幅度。因此，α-肾上腺素能激动剂可能根据电流诱导机制对Iti产生抑制或刺激作用。对OAP幅度的其他影响可能是通过对净外向电流的作用介导的动作电位持续时间变化所诱导的。哌唑嗪可能通过对Iti的作用来抑制OAP，这种作用独立于α-肾上腺素能或局部麻醉作用。
