四肽FMRFa对大鼠心室肌Na^+/Ca^(2+)交换的抑制

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

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。

AIM To study the effects of Phe Met Arg Phe NH 2 (FMRFa) on Na +/Ca 2+ exchange and its specificity for Na +/Ca 2+ exchange in rat ventricular myocytes. METHODS Na +/Ca 2+ 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 +/Ca 2+ exchange was observed in rat ventricular myocytes. Inward and outward I Na +/Ca 2+ were inhibited by 60 1% and 56 5%, respectively, at highest concentration (100 μmol·L -1 ) and its IC 50 were 20 μmol·L -1 and 34 μmol·L -1 in inward and outward I Na +/Ca 2+ , respectively. Inward and outward I Na +/Ca 2+ were inhibited 38 7% and 34 9%, respectively, at FMRFa 5 μmol·L -1 . FMRFa 5 μmol·L -1 and 20 μmol·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 +/Ca 2+ exchange in intact rat ventricular myocytes.