RP58866对哺乳动物心室肌细胞跨膜钾电流的作用(英文)

Effects of RP58866 on transmembrane K^+ currents in mammalian ventricular myocytes

目的:研究RP58866对于豚鼠或犬分离心室肌细胞I_K,I_(to),和I_(Kl)的影响。方法:采用全细胞膜片箝技术。结果:在-100 mV时,RP58866以浓度依赖方式明显减少了豚鼠心室肌细胞I_(kl),其IC_(50)为(3.4±0.8)μmol·L^(-1)(n=6)。在犬心室肌细胞,RP58866可明显抑制I_(to),其IC_(50)为(2.3±0.5)μmol·L^(-1)。RP58866 100μmol·L^(-1)阻断豚鼠的心室肌细胞I_K,在+40mv时使I_(Kstep)减少(58±13)％,其IC_(50)为(7.5±0.8)μmol·L^(-1),I_(Ktail)减少(86±17)％,其IC_(50)为(3.5±0.9)μmol·L^(-1)。尾电流分析表明,RP58866对I_(Kr)和I_(Ks)均有阻断作用。结论:RP58866对心肌细胞的I_(Kl)和I_(to),I_K均有抑制作用,而不是一种特殊的I_(Kl)抑制剂。

AIM: To determine effects of RP58866 on inward rectifier K+ current ( IKI ), transient outward K+ current (Ito) and delayed outward rectifier K+ current (IK.) in isolated cardiac myocytes. METHODS: In isolated ventricular myocytes of guinea pig and dog, the effect of RP58866 on IKI, Ito, and IK were observed by the whole cell voltage-clamp technique. RESULTS: RP58866 decreased IK1 in a concentration-dependent manner, with an IC50 of (3.4 ± 0.8) μmol·L-1(n = 6) at - 100 mV in guinea pig ventricular cells. In dog ventricular myocytes, RP58866 inhibited Ito with IC50 of (2.3 ± 0.5) μmol · L-1 at + 40 mV. In guinea pig ventricular cells, RP58866 at 100 μmol·L-1 decreased Ik:IKstep by (58± 13) % at + 40 mV, and IKtail by (86 ± 17) %, respectively. RP58866 inhibited IKstep with an IC50 of (7.5 ± 0.8) μmol·L-1, and IKtail with an IC50 of (3.5±0.9) μmol · L-1. The envelope of tail analysis suggested that both IKr and IKs were inhibited. CONCLUSION: RP58866 inhibits IKI, Ito, and IK in cardiac myocytes with a similar potency, and is not a specific IKI inhibitor.