17β-雌二醇对豚鼠心室肌细胞L型钙电流的抑制作用

Inhibitory effects of 17β-estradiol on L-type Ca^(2+) currents in isolated guinea-pig ventricular myocytes

目的观察17β-雌二醇对豚鼠心室肌细胞L型钙电流的影响及其与雌激素受体(estrogen receptor,ER)的关系。方法酶机械法分离豚鼠单个心室肌细胞;膜片钳全细胞模式观察17β-雌二醇对单个心室肌细胞L型钙电流(ICa-L)的影响,并通过加入雌激素受体阻断剂tamoxifen(TAM)研究该作用与雌激素受体的关系。结果 17β-雌二醇(10-9～10-7mol.L-1)使ICa-L峰电流密度值从(-3.5±0.6)pA.pF-1分别减少至(-2.4±0.3)pA.pF-1、(-1.9±0.3)pA.pF-1和(-1.1±0.3)pA.pF-1(与对照组比较,均为P<0.01,n=5)。TAM(10-7 mol.L-1)预处理后,17β-雌二醇(10-7mol.L-1)使ICa-L峰电流密度值从(-3.5±0.6)pA.pF-1减少到(-1.0±0.2)pA.pF-1(与对照组比较,P<0.01,n=5),与未应用TAM(10-7 mol.L-1)预处理时比较,ICa-L峰电流密度值无变化(P>0.05,n=5)。结论 17β-雌二醇抑制豚鼠心室肌细胞ICa-L的作用呈浓度依赖性,雌激素受体阻断剂TAM不能阻断17β-雌二醇对豚鼠心室肌细胞ICa-L的抑制作用,提示17β-雌二醇对ICa-L的抑制作用可能与ER作用无关。

Aim To observe the effects of 17β-estradiol on L-type Ca2＋ currents（ICa-L） and investigate the possible involvement of estrogen receptor（ER）.Methods Ventricular myocytes were isolated from guinea-pigs heart,and ICa-L was measured with whole cell patch-clamp technique.Results The results showed that 17β-estradiol（10-9~10-7 mol·L-1） decreased the peak current density of ICa-L from（-3.5±0.6） pA·pF-1 to（-2.4±0.3） pA·pF-1,（-1.9±0.3） pA·pF-1 and（-1.1±0.3） pA·pF-1,respectively（P0.01）,compared with control group.Myocytes were then pre-treated with the estrogen receptor antagonist TAM（10-7 mol·L-1）,17β-estradiol（10-7 mol·L-1） still decreased the peak current density of ICa-L from（-3.5±0.6） pA·pF-1 to（-1.0±0.2） pA·pF-1（P0.01）,compared with control group.The peak current density of ICa-L had no significant difference compared with that of 17β-estradiol（10-7 mol·L-1） alone（without TAM pre-treatment）（P0.05）.Conclusions 17β-estradiol can inhibit ICa-L in isolated guinea-pig ventricular myocytes in a concentration-dependent manner.ER is not likely involved in the inhibition of ICa-L induced by 17β-estradiol in cardiac myocytes in this condition.