Effect of angiotensin II type I receptor on delayed rectifier potassium current in catecholaminergic CATH.a cells

AIM: To study the modulatory effects of angiotensin 11 (Ang 11) on the delayed rectifier potassium (Kv) current (I-Kv) and its underlying intracellular mechanism in the catecholaminergic system of rats. METHODS: AT(1) and AT(2) receptors of the differentiated and undifferentiated CATH.a cells were determined by radioligands binding assay. The I-Kv, was recorded with the whole cell patch-clamp configuration in voltage clamp mode on CATH.a cells. RESULTS: The Ang Il receptor proteins including AT(1) and AT(2) receptors were expressed in CATH.a cells, and the number of the former was significantly more than the latter (P<0.01). The I-Kv, of CATH.a cells was reduced by superfusion with the Ang II (100 nmol/L) (P<0.05) in the presence of the AT(2) receptor antagonist PD123319, but was not affected by only superfusion with PD123319. The effect of Ang 11 on I-Kv, in CATH.a cells was completely inhibited by addition of AT(1) receptor antagonist losartan. Superfusion with Ang 11 (100 nmol/L) plus U73122, an inhibitor of phospholipase C (PLC) in the presence of PD123319 had no effect on the I-Kv, [(20.2 +/- 2.8) pA/pF]. Ang II-induced reduction of I-Kv, was attenuated (P<0.05) but not abolished by PKC inhibitor calphostin C (Cal) and selective CaMK 11 inhibitor KN-93 (10 mumol/L) respectively. However, I-Kv, reduction was completely abolished by superfusion with both Cal and KN-93. CONCLUSION: The inhibition of Kv currents in CATH.a cells by Ang 11 is mediated by AT(1) receptor, and the PLC, PKC and CaMK 11 may be involved in signal transduction of AT(1) receptor. The differentiated CATH.a cell is a useful cell model to study Ang 11 receptor-mediated functional modulation of