Malchow R P, Qian H, Ripps H
Lions of Illinois Eye Research Institute, Department of Ophthalmology and Visual Sciences, Chicago.
J Gen Physiol. 1994 Dec;104(6):1039-55. doi: 10.1085/jgp.104.6.1039.
The cinchona alkaloids quinine and quinidine have been shown to block a broad range of voltage-gated membrane conductances in a variety of excitable tissues. Using the whole-cell version of the patch clamp technique, we examined the effects of these compounds on voltage-dependent currents from horizontal cells dissociated enzymatically from the all-rod retina of the skate. We report here a novel and unexpected action of quinine and quinidine on isolated horizontal cells. In addition to blocking several of the voltage-activated currents of these cells, the introduction of the alkaloids evoked a large outward current when the cells were held at depolarized potentials. Using tail current analysis, the reversal potential of the outward current was close to O mV, and the current was markedly suppressed by extracellularly applied cobalt, acetate, and halothane. Depolarization in the presence of quinine also permitted entry into the cells of extracellularly applied Lucifer yellow (MW = 443 D), whereas a 3-kD fluorescein-dextran complex was excluded. These findings suggest that the large, apparently nonselective conductance induced by quinine and quinidine results from the opening of hemi-gap junctional channels.
金鸡纳生物碱奎宁和奎尼丁已被证明能在多种可兴奋组织中阻断广泛的电压门控膜电导。使用膜片钳技术的全细胞版本，我们研究了这些化合物对从鳐鱼全视杆视网膜酶解分离的水平细胞的电压依赖性电流的影响。我们在此报告奎宁和奎尼丁对分离的水平细胞的一种新的意外作用。除了阻断这些细胞的几种电压激活电流外，当细胞保持在去极化电位时，生物碱的引入会诱发一个大的外向电流。使用尾电流分析，外向电流的反转电位接近0 mV，并且该电流被细胞外施加的钴、乙酸盐和氟烷显著抑制。在奎宁存在下的去极化也允许细胞外施加的荧光素黄（分子量 = 443 D）进入细胞，而3-kD的荧光素 - 葡聚糖复合物则被排除在外。这些发现表明，奎宁和奎尼丁诱导的大的、明显非选择性的电导是由半间隙连接通道的开放引起的。
