Watanabe Yasuhide, Koide Yuuki, Kimura Junko
Division of Pathophysiology, Basic Nursing, Hamamatsu University School of Medicine, Japan.
J Pharmacol Sci. 2006 Sep;102(1):7-16. doi: 10.1254/jphs.fmj06002x2.
Using the whole-cell voltage clamp, we examined acute effects of various agents on Na(+)/Ca(2+) exchange current (I(NCX)) in guinea-pig cardiac ventricular cells and transfected cells. Among the antiarrhythmic drugs, amiodarone, bepridil, dronedarone, cibenzoline, azimilide, and aprindine inhibited I(NCX) in a concentration-dependent manner. We also investigated the effects on NCX of 2,3-buanedione monoxim (BDM) and selective NCX inhibitors such as KB-R7943, SEA0400, and SN-6. The presence of trypsin in the pipette solution attenuated the inhibitory effects on NCX of amiodarone, bepridil, and BDM, suggesting that these drugs inhibit NCX from the cytosolic side. In contrast, the trypsin-insensitive NCX inhibitors were aprindine, azimilide, dronedarone, cibenzoline, KB-R7943, SEA0400, and SN-6. KB-R7943, SEA0400, and SN-6 suppressed the uni-directional outward I(NCX) more potently than the uni-directional inward I(NCX). The mechanism of this mode-dependency is unknown, but is suggested to be related to intracellular Na(+) concentration.
我们使用全细胞膜片钳技术，研究了多种药物对豚鼠心室肌细胞和转染细胞中钠钙交换电流（I(NCX)）的急性作用。在抗心律失常药物中，胺碘酮、苄普地尔、决奈达隆、西苯唑啉、阿齐利特和茚满丙二胺以浓度依赖的方式抑制I(NCX)。我们还研究了2,3-丁二酮一肟（BDM）以及选择性钠钙交换抑制剂如KB-R7943、SEA0400和SN-6对钠钙交换的影响。移液管溶液中存在胰蛋白酶可减弱胺碘酮、苄普地尔和BDM对钠钙交换的抑制作用，提示这些药物从胞质侧抑制钠钙交换。相反，对胰蛋白酶不敏感的钠钙交换抑制剂有茚满丙二胺、阿齐利特、决奈达隆、西苯唑啉、KB-R7943、SEA0400和SN-6。KB-R7943、SEA0400和SN-6对单向外向I(NCX)的抑制作用比对单向内向I(NCX)更强。这种模式依赖性的机制尚不清楚，但提示与细胞内钠离子浓度有关。
