Niu Chun-Feng, Watanabe Yasuhide, Iwamoto Takahiro, Yamashita Kanna, Satoh Hiroshi, Urushida Tuyoshi, Hayashi Hideharu, Kimura Junko
Department of Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Hondayama, Hamamatsu, Shizuoka, 431-3192, Japan.
Ann N Y Acad Sci. 2007 Mar;1099:534-9. doi: 10.1196/annals.1387.037.
We examined the effect of SN-6 on the Na+/Ca2+ exchanger (NCX) current (I(NCX)) and other membrane currents in isolated guinea pig ventricular myocytes using the whole-cell voltage clamp technique. SN-6 suppressed the bidirectional I(NCX) in a concentration-dependent manner. The IC50 values of SN-6 were 2.3 microM and 1.9 microM for the outward and inward components of the bidirectional I(NCX), respectively. On the other hand, SN-6 suppressed the unidirectional outward I(NCX) more potently than the inward I(NCX), with an IC(50) value of 0.6 microM. SN-6 at 10 microM inhibited the unidirectional inward I(NCX) by only 22.4 +/- 3.1%. SN-6 suppressed I(NCX) more potentially when intracellular Na+ concentration became higher. SN-6 inhibited I(Na), I(Ca), I(Kr), I(Ks), and I(K1) by about 13%, 34%, 33%, 18%, and 13%, respectively. SN-6 shortened the action potential duration (APD) by about 34% and 25% at APD(50) and APD(90), respectively. These results indicate that SN-6 inhibits NCX in a similar manner to that of KB-R7943. SN-6 and KB-R7943 inhibit the unidirectional outward I(NCX) more potently than the unidirectional inward I(NCX). Both drugs inhibit NCX in an intracellular Na+ concentration-dependent manner. However, SN-6 affected other membrane currents less potently than KB-R7943.
我们使用全细胞膜片钳技术研究了SN - 6对分离的豚鼠心室肌细胞中钠钙交换体（NCX）电流（I(NCX)）及其他膜电流的影响。SN - 6以浓度依赖的方式抑制双向I(NCX)。对于双向I(NCX)的外向和内向成分，SN - 6的半数抑制浓度（IC50）值分别为2.3微摩尔/升和1.9微摩尔/升。另一方面，SN - 6对单向外向I(NCX)的抑制作用比对内向I(NCX)更强，IC(50)值为0.6微摩尔/升。10微摩尔/升的SN - 6仅抑制单向内向I(NCX) 22.4±3.1%。当细胞内钠离子浓度升高时，SN - 6对I(NCX)的抑制作用更显著。SN - 6分别抑制I(Na)、I(Ca)、I(Kr)、I(Ks)和I(K1)约13%、34%、33%、18%和13%。SN - 6使动作电位时程（APD）在APD(50)和APD(90)时分别缩短约34%和25%。这些结果表明，SN - 6抑制NCX的方式与KB - R7943相似。SN - 6和KB - R7943对单向外向I(NCX)的抑制作用比对单向内向I(NCX)更强。两种药物均以细胞内钠离子浓度依赖的方式抑制NCX。然而，SN - 6对其他膜电流的影响比KB - R7943弱。
