四肽FMRFa对大鼠心室肌Na+/Ca2+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(I_Na⁺/Ca²⁺)和其他离子通道电流。结果　FMRFa对大鼠心室肌细胞I_Na⁺/Ca²⁺呈浓度依赖性抑制，100μmol·L^-1浓度时抑制内向和外向I_Na⁺/Ca²⁺密度分别达60.1%和56.5%，对内向电流及外向电流的IC₅₀分别为20μmol·L^-1和34μmol·L^-1。FMRFa5μmol·L^-1抑制I_Na⁺/Ca²⁺内向和外向电流密度分别为38.7%和34.9%，但FMRFa5μmol·L^-1及20μmol·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+/Ca2+ 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 I_Na⁺/Ca²⁺ were inhibited by 60.1% and 56.5%, respectively, at highest concentration (100 μmol·L^-1) and its IC₅₀ were 20 μmol·L^-1 and 34 μmol·L^-1 in inward and outward I_Na⁺/Ca²⁺, respectively. Inward and outward I_Na⁺/Ca²⁺ 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⁺/Ca²⁺ exchange in intact rat ventricular myocytes.