Characterization of SN-6, a novel Na+/Ca2+ exchange inhibitor in guinea pig cardiac ventricular myocytes
Characterization of SN-6, a novel Na+/Ca2+ exchange inhibitor in guinea pig cardiac ventricular myocytes
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DOI：
10.1016/j.ejphar.2007.06.033
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发表时间：
2007-11-14
影响因子：
5
通讯作者：
Kimura, Junko
中科院分区：
文献类型：
--
作者：
Niu, Chun-Feng;Watanabe, Yasuhide;Kimura, Junko
采用全细胞电压钳技术，观察了新型苄氧基苯基钠钙交换（Na ~+/Ca ~（2+）exchange，NCX）抑制剂SN-6对豚鼠心室肌细胞Na ~+/Ca ~（2+）交换电流（I-NCX）及其它膜电流的影响。SN-6以浓度依赖性方式抑制I-NCX。SN-6对双向I-NCX的外向和内向成分的IC 50值分别为2.3 μ M和1.9 μ M。另一方面，SN-6抑制外向单向I-NCX比内向单向I-NCX更有效（IC 50值为0.6 μ M）。10 μ M的SN-6仅抑制22.4 +/-3.1%的单向内向I-NCX。当细胞内Na+浓度较高时，SN-6和KB-R7943更有效地抑制I-NCX。因此，两种药物均以细胞内Na+浓度依赖性方式抑制NCX。通过移液管溶液细胞内应用胰蛋白酶并没有改变SN-6对I-NCX的阻断作用。因此，SN-6被归类为细胞内胰蛋白酶不敏感的NCX抑制剂。SN-6在10 μ M时对I-Na、I-Ca、I-K和I-KI的抑制率分别约为13%、34%、33%和13%。SN-6在10 μ M时使50%复极化时的动作电位时程（APD（50））缩短约34%，使90%复极化时的动作电位时程（APD（90））缩短约25%。这些结果表明SN-6以与KB-R7943相似的方式抑制NCX。然而，SN-6在10 μ M影响其他膜电流不如KB-R7943。(c)2007 Elsevier B. V.保留所有权利。
We examined the effect of SN-6, a new benzyloxyphenyl Na+/Ca2+ exchange (NCX) inhibitor on the Na+/Ca2+ exchange current (I-NCX) and other membrane currents in isolated guinea pig ventricular myocytes using the whole-cell voltage-clamp technique. SN-6 suppressed I-NCX in a concentration-dependent manner. The IC50 values of SN-6 were 2.3 mu M and 1.9 mu M for the outward and inward components of the bi-directional I-NCX, respectively. On the other hand, SN-6 suppressed the outward uni-directional I-NCX more potently (IC50 value of 0.6 mu M) than the inward uni-directional I-NCX. SN-6 at 10 mu M inhibited the uni-directional inward I-NCX by only 22.4 +/- 3.1%. SN-6 and KB-R7943 suppressed I-NCX more potently when intracellular Na+ concentration was higher. Thus, both drugs inhibit NCX in an intracellular Na+ concentration-dependent manner. Intracellular application of trypsin via a pipette solution did not change the blocking effect of SN-6 on I-NCX. Therefore, SN-6 is categorized as an intracellular-trypsin-insensitive NCX inhibitor. SN-6 at 10 mu M inhibited I-Na, I-Ca, I-K and I-KI by about 13%, 34%, 33% and 13%, respectively. SN-6 at 10 mu M shortened the action potential duration at 50% repolarization (APD(50)) by about 34%, and that at 90% repolarization (APD(90)) by about 25%. These results indicate that SN-6 inhibits NCX in a similar manner to that of KB-R7943. However, SN-6 at 10 mu M affected other membrane currents less potently than KB-R7943. (c) 2007 Elsevier B.V. All rights reserved.