肾上腺髓质素对豚鼠心室肌细胞L-型钙通道的调制(英文)

Inhibitory effect of adrenomedullin on L-type calcium currents in guinea-pig ventricular myocytes

应用全细胞膜片钳技术研究了肾上腺髓质素 (ADM )对豚鼠心室肌细胞L 型钙电流 (ICa ,L)的影响及其信号传导机制。结果发现 :ADM ( 1～ 10 0nmol/L)浓度依赖性抑制ICa,L(P <0 0 5 ) ,并可被ADM特异受体阻断剂ADM2 2 52 ( 10 0nmol/L)完全阻断。用蛋白激酶A特异拮抗剂H 89( 10 μmol/L)预处理 ,对ADM抑制ICa ,L的作用无影响。但用蛋白激酶C (PKC)特异性拮抗剂PKC19 36 预处理 ,可完全阻断ADM的抑制效应 ;而PKC特异性激动剂PMA则可以模仿ADM的抑制效应 (P <0 0 5 )。上述结果提示 :ADM作用于特异性ADM受体可浓度依赖性地抑制豚鼠心室肌细胞ICa ,L,而此作用可能是PKC介导的。

The effects of adrenomedullin (ADM) on the L-type calcium currents (I Ca,L) and the mechanism of the signal transduction process were studied. Enzymatically isolated guinea-pig ventricular myocytes were used to measure I Ca,L with whole-cell patch-clamp techniques. ADM at the concentrations of 1～100 nmol/L decreased I Ca,L in a dose-dependent manner (P<0.05). ADM 22-52 (100 nmol/L), a specific ADM-receptor antagonist, completely abolished the ADM-induced inhibition of I Ca,L. Pretreatment of the cells with H-89 (10 μmol/L) , a specific PKA inhibitor, did not attenuate the effects of ADM. Intracellular application of 10 μmol/L PKC 19-36 , a specific PKC inhibitor, prevented the ADM-induced inhibition of the I Ca,L, while the specific PKC activator PMA could mimic the effects of ADM on the I Ca,L. PMA (1 μmol/L) decreased the I Ca,L by 32.26±4.20% (P<0.05). These findings indicate that ADM can inhibit the I Ca,L in guinea-pig ventricular myocytes, and the inhibition is mediated by the specific ADM-receptor and an activation of protein kinase C.