摘要
Objective To study the cellular mechanism of the effect of Ang Ⅱ on ICa,L in single guinea-pig ventricular cells by using losartan and 1-(5-Isoquinolinylsulfonyl)-2-Methyl-Piperazine (H-7) as the Ang Ⅱ type 1 receptor (AT1) inhibitor and protein kinase C inhibitor, respectively.Methods Patch clamp techniques were used to study the cellular mechanism of the effect of Ang Ⅱ on ICa,L in single guinea-pig ventricular cells.Results In the whole cell patch clamp recording model, Ang Ⅱ stimulated ICa,L in a concentration dependent manner; the maximal effect was obtained at 100?nmol/L (n=9). At 30?nmol/L, Ang Ⅱ stimulated peak ICa,L from 11.3±0.6?pA/pF to 15.3±0.6?pA/pF (at +10?mV, n=9, P<0.05). 100?nmol/L Losartan, a specific AT1 receptor inhibitor, had no effect on ICa,L (n=9), but the effect of Ang Ⅱ on ICa,L was inhibited by 100?nmol/L Losartan. Ang Ⅱ on ICa,L was also inhibited by 20?μmol/L H-7, a specific protein kinase C inhibitor, whereas H-7 alone has no effect on ICa,L (n=9).Conclusion Ang Ⅱ stimulates ICa,L in guinea-pig ventricular cells by binding to AT1 through a transduction pathway involving protein kinase C.
目的 以往的研究表明血管紧张素Ⅱ (AngⅡ )对心室肌细胞L型钙流 (ICa,L)的影响及作用机制尚有争议。本文应用AngⅡ 1型受体 (AT1)阻滞剂Losartan和蛋白激酶C(PKC)抑制剂H 7来研究AngⅡ对单个豚鼠心室肌细胞ICa ,L的作用及机制。方法 应用膜片钳技术研究AngⅡ对单个豚鼠心室肌细胞ICa ,L影响的细胞机制。结果 结果表明 ,在膜片钳全细胞记录模式 ,AngⅡ刺激ICa ,L,呈浓度依赖性 ,最大作用浓度为 10 0nmol/L (n =9)。30nmol/L的AngⅡ使ICa ,L峰电流由 11 3± 0 6pA/pF增大为 15 3± 0 6pA/pF( +10mV ,n =9,P <0 0 5)。 10 0nmol/L的Losartan本身对ICa ,L无影响 ,但可抑制AngⅡ对ICa,L的作用。AngⅡ对ICa,L的作用也能被 2 0nmol/L的H 7所抑制 ,而H 7本身对ICa,L无影响。结论 以上结果提示AngⅡ经AngⅡ 1型受体刺激ICa,L,这一作用经由PKC介导而实现。
