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 recep...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.展开更多
文摘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.