MEMBRANE ELECTRICAL-PROPERTIES OF VESICULAR NA-CA EXCHANGE INHIBITORS IN SINGLE ATRIAL MYOCYTES
MEMBRANE ELECTRICAL-PROPERTIES OF VESICULAR NA-CA EXCHANGE INHIBITORS IN SINGLE ATRIAL MYOCYTES
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DOI：
10.1161/01.res.59.4.381
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发表时间：
1986-10-01
影响因子：
20.1
通讯作者：
HUME, JR
中科院分区：
文献类型：
--
作者：
BIELEFELD, DR;HADLEY, RW;HUME, JR
负载na的单个青蛙心房细胞产生的膜电流变化类似于最初在负载na的心脏浦肯野纤维中观察到的蠕变电流。暴露于Na离子载体，莫能菌素，用于诱导分离心房细胞的蠕变电流。评估了心肌蠕变电流对三种化合物的敏感性，这三种化合物已被证明是分离的肌上皮囊泡中Na-Ca交换通量活性的抑制剂。十二胺、醌和酰胺类类似物3',4' -二氯苯甲胺阻断蠕变电流的浓度远低于阻断肌层囊泡中na依赖性钙吸收所需的浓度。估计对心肌蠕变电流的抑制Ki′s为3 μ。M代表十二胺，10亩。M代表阿奎宁，4亩。M代表3 ",4 " -二氯苯苄胺。蠕变电流对这些化合物的敏感性与蠕变电流可能代表Na-Ca交换载体的电活性的假设是一致的。在另外一系列的实验中，通过检测这些化合物对心肌膜通道的影响来测试它们的相对特异性。十二胺和3',4' -二氯苯甲胺在相同的浓度范围内抑制心肌Ca和K电流，在这种浓度范围内发生交换活性阻断。这些结果严重质疑使用这些交换载体抑制剂作为选择性实验探针来定义Na-Ca交换在各种生理过程中的作用。
Na-loading single frog atrial cells produce changes in membrane currents that are similar to the creep currents originally observed in Na-loaded cardiac Purkinje fibers. Exposure to the Na ionophore, monensin, was used to induce creep currents in isolated atrial cells. The sensitivity of myocardial creep currents to three compounds that have been shown to be inhibitors of Na-Ca exchange flux activity in isolated sarcolemmal vesicles was assessed. Dodecylamine, quinacrine, and the amiloride analog, 3'',4''-dichlorobenzamil block creep currents at concentrations well below those required to block Na-dependent Ca uptake in sarcolemmal vesicles. The estimated Ki''s for inhibition of myocardial creep currents were 3.mu.M for dodecylamin, 10.mu.M for quinacrine, and 4.mu.M for 3'',4''-dichlorobenzamil. The sensitivity of creep currents to these compounds is consistent with the hypothesis that creep currents may represent the electrogenic activity of a Na-Ca exchange carrier. In an additional series of experiments, the relative specificity of these compounds was tested by examining their effects on myocardial membrane channels. Both dodecylamine and 3'',4''-dichlorobenzamil were found to inhibit myocardial Ca and K currents over the same range of concentrations in which block of exchange activity occurs. These results seriously question the use of these exchange carrier inhibitors as selective experimental probes for defining the role of Na-Ca exchange in various physiological processes.