四肽FMRFa对大鼠心室肌Na^＋／Ca^2＋交换的抑制

目的　研究四肽FMRFa对大鼠单个心室肌细胞Na /Ca2 交换的作用。方法　用膜片钳全细胞记录法测定成年大鼠心室肌细胞Na /Ca2 交换电流 (INa /Ca2 )和其他离子通道电流。结果　FMRFa对大鼠心室肌细胞INa /Ca2 呈浓度依赖性抑制 ,10 0 μmol·L-1浓度时抑制内向和外向INa /Ca2 密度分别达 6 0 1%和 5 6 5 % ,对内向电流及外向电流的IC50 分别为 2 0 μmol·L-1和 34μmol·L-1。FMRFa 5 μmol·L-1抑制INa /Ca2 内向和外向电流密度分别为 38 7%和 34 9% ,但FMRFa 5 μmol·L-1及 2 0 μmol·L-1对L型钙电流、钠电流、瞬时外向电流和内向整流钾电流均无显著抑制作用。结论　FMRFa对大鼠心室肌细胞是一个特异性Na /Ca2 交换抑制剂。

INHIBITION OF Na~ /Ca~(2 ) EXCHANGE BY TETRAPEPTIDE FMRFa IN INTACT RAT VENTRICULAR MYOCYTES

AIM: To study the effects of Phe-Met-Arg-Phe-NH2(FMRFa) on Na+/Ca2+ exchange and its specificity for Na+/Ca2+ exchange in rat ventricular myocytes. METHODS: Na+/Ca2+ exchange current and other currents of ion channels were measured using whole cell voltage clamp techniques. RESULTS: A dose-related inhibition of tetrapeptide FMRFa on Na+/Ca2+ exchange was observed in rat ventricular myocytes. Inward and outward INa+/Ca2+ were inhibited by 60.1% and 56.5%, respectively, at highest concentration (100 mumol.L-1) and its IC50 were 20 mumol.L-1 and 34 mumol.L-1 in inward and outward INa+/Ca2+, respectively. Inward and outward INa+/Ca2+ were inhibited 38.7% and 34.9%, respectively, at FMRFa 5 mumol.L-1. FMRFa 5 mumol.L-1 and 20 mumol.L-1 did not affect L-type calcium current, sodium current, transient outward current and inward rectifier potassium current. CONCLUSION: These data indicate that FMRFa is a specific inhibitor of Na+/Ca2+ exchange in intact rat ventricular myocytes.