Mechanisms of actions of organic and inorganic Ca antagonists.

有机和无机钙拮抗剂的影响进行了研究，通过应用于分散的单个平滑肌细胞的膜片钳和全细胞电压钳技术。在家兔门静脉记录到三种不同类型的单通道电流（<K_L>、<K_M>和<K_S>）。均为K选择性电流，<K_L><K_S>依赖于和<Ca_i>。<K_M>在<Ca_o>2.8 mM时，被激活并显示无电压依赖性<Ca_o>。通道的这种行为<K_M>迄今尚未得到证实，可能有助于静息膜电流。有机钙拮抗剂硝苯地平、尼索地平对钙离子无作用<K_L>，镁、钡则有抑制作用<K_L>。Mg降低了“表观”单通道电流的幅度，Ba降低了通道开放的频率，但不影响幅度。这些结果表明，高浓度的有机钙拮抗剂引起的膜去极化与微电极实验中观察到的，是不是由于抑制。<K_L>有机钙拮抗剂对宏观膜电流的影响也进行了研究。去极化脉冲诱发内向电流，尼卡地平、地尔硫卓和维拉帕米抑制内向电流，抑制顺序为尼卡地平、维拉帕米、地尔硫卓。维拉帕米以频率依赖性方式抑制内向电流。相反，尼卡地平抑制电流，在电压依赖性的方式。因此，平滑肌细胞的静息膜电位与Ca拮抗剂存在下观察到的内向电流抑制密切相关。在兔回肠纵肌和门静脉的平滑肌细胞中，这些钙拮抗剂当应用于膜的细胞内侧时没有作用，因此，膜的外表面可能参与这种作用。

The effects of organic and inorganic Ca antagonists were investigated by means of the patch and whole cell voltage clamp techniques applied to dispersed single smooth muscle cells. Three different types of single channel currets ( <K_L> , <K_M> and <K_S> ) were recorded from the rabbit portal vein. All were K-selective currents, and <K_L> and <K_S> were depended on <Ca_i> . <K_M> was activated by <Ca_o> and showed no voltage-dependency at 2.8 mM <Ca_o> . Such behavior of the <K_M> channel has not yet heretofore been evidenced and possibly contributes the resting membrane currents. While organic Ca antagonists such as nifedipine or nisoldipine had no actions on <K_L> , Mg and Ba did inhibit <K_L> . Mg reduced the amplitude of the "apparent" single channel current and Ba reduced frequency of the channel opening, without affecting the amplitude. These results suggest that the membrane depolarization induced by a high concentration of the organic Ca antagonists observed with the microelectrode experiments, was not due to an inhibition of <K_L> .Effects of organic Ca antagonists on the macroscopic membrane currents were also investigated. The inward current was evoked by the depolarizing pulse and nicaldipine, diltiazem and verapamil inhibited the inward current; sequence being nicardipine verapamil diltiazem. Verapamil inhibited the inward current, in a frequency, use-dependent manner. In contrast, nicardipine inhibited the current, in a voltage-dependent manner. Thus, resting membrane potentials of the smooth muscle cells were closely linked to inhibition of the inward current seen in the presence of the Ca antagonists. In smooth muscle cells of the rabbit ileal longitudinal muscle and portal vein, these Ca antagonists had no effect when applied to the intracellular side of the membrane, therefore, the outer surface of the membrane is probably involved in such effects.