Effect of angiotensin Ⅱ type 1 receptor on delayed rectifier potassium current in catecholaminergic

AIM: To study the modulatory effects of angiotensin Ⅱ(Ang Ⅱ) on the delayed rectifier potassium (Kv) current (IKv) and its underlying intracellular mechanism in the catecholaminergic system of rats. METHODS: AT1 and AT2 receptors of the differentiated and undifferentiated CATH.a cells were determined by radioligands binding assay. The IKv was recorded with the whole cell patch-clamp configuration in voltage clamp mode on CATH.a cells. RESULTS： The AngⅡ receptor proteins including AT1 and AT2 receptors were expressed in CATH.a cells, and the number of the former was significantly more than the latter (P<0.01). The IKv of CATH.a cells was reduced by superfusion with the AngⅡ(100nmol/L) (P<0.05) in the presence of the AT2 receptor antagonist PD123319, but was not affected by only superfusion with PD123319. The effect of AngⅡ on IKv in CATH.a cells was completely inhibited by addition of AT1 receptor antagonist losartan. Superfusion with AngⅡ(100nmol/L) plus U73122, an inhibitor of phospholipase C(PLC) in the presence of PD 123319 had no effect on the IKv [(20.2±2.8)pA/pF]. AngⅡ-induced reduction of IKv was attenuated (P<0.05) but not abolished by PKC inhibitor calphostin C (Cal) and selective CaMK Ⅱ inhibitor KN-93 (10μmol/L) respectively. However, IKv reduction was completely abolished by superfusion with both Cal and KN-93. CONCLUSION: The inhibition of Kv currents in CATH.a cells by AngⅡ is mediated by AT1 receptor, and the PLC, PKC and CaMK Ⅱ may be involved in signal transduction of AT1 receptor.The differentiated CATH.a cell is a useful cell model to study AngⅡ receptor-mediated functional modulation of catecholaminergic system.

完成机构：[1]DepartmentofPhysiology,SchoolofMedicine,Xi＇anJiaotongUniversity,Xi＇an710061,China [2]DepartmentofPhysiology,SchoolofMedicine,Xi＇anJiaotongUniversity,Xi＇an710061,China