[乙胺碘呋酮对绵羊心脏浦肯野细胞电生理参数的影响。钠通道的频率依赖性阻滞]

[Effect of ethmozin on the electrophysiologic parameters of Purkinje cells in the sheep heart. The frequency-dependent blockade of sodium channels].

作者信息

Undrovinas A I, Sawicki G J, Nesterenko V V, Rosenshtraukh L V, Arnsdorf M F

出版信息

Biull Vsesoiuznogo Kardiol Nauchn Tsentra AMN SSSR. 1986;9(2):8-15.

Abstract

The effect of ethmozin (E) on action potential (AP) duration (ADP90, APD50), AP upstroke velocity (Vmax) and cable properties (Ri, Rm, Rin, Cm, lambda m, tau m) was studied. Vmax was significantly reduced by E (0.2 to 5 mkM). Duration of AP plateau (APD50) was more sensitive to E than APD90. Thus, application of 0.5 mkM E resulted in 30% decrease of APD90 and 60% of APD50. This suggested that E not only inhibits INa, what is reflected by Vmax reduction, but also can affect other currents involved in plateau phase. Cable properties remained unchanged in the wide concentration range of E. Blockade of Vmax by E was use-dependent. Uptake rates of ethmozin by sodium channel for different stimulation frequencies were estimated and kinetic binding and unbinding constants (k = 40322 M-1 ms-1; 1 = 7.17 X 10(-5) ms-1) with unguarded receptor were calculated using novel drug-channel interaction model (Starmer and Grant, 1985).

摘要

研究了乙吗噻嗪（E）对动作电位（AP）时程（ADP90、APD50）、AP上升速度（Vmax）和电缆特性（Ri、Rm、Rin、Cm、λm、τm）的影响。E（0.2至5μM）可显著降低Vmax。AP平台期时程（APD50）对E比APD90更敏感。因此，应用0.5μM E可使APD90降低30%，APD50降低60%。这表明E不仅抑制INa（这由Vmax降低反映），还可影响平台期涉及的其他电流。在较宽的E浓度范围内，电缆特性保持不变。E对Vmax的阻断具有使用依赖性。使用新型药物-通道相互作用模型（Starmer和Grant，1985）估计了不同刺激频率下钠通道对乙吗噻嗪的摄取速率，并计算了与无保护受体的动力学结合和解离常数（k = 40322 M-1 ms-1；1 = 7.17×10-5 ms-1）。