Modulation of delayed rectifier potassium current by angiotensin II in CATH.a cells

Abstract

Angiotensin II (Ang II) modulates, via Ang II type 1 (AT 1) receptors, the activity of brain catecholaminergic neurons. Here we utilized catecholaminergic CATH.a cells to define the effects of Ang II on delayed rectifier K + current ( I Kv), one of the factors that determines changes in neuronal activation. Receptor binding analyses demonstrated the presence of AT 1 receptors in CATH.a cells. Whole cell voltage clamp experiments in these cells revealed that Ang II (100 nM) produced a significant inhibition of I Kv, that was abolished by the AT 1 receptor blocker, losartan (1 μM), or by inhibition of phospholipase C (PLC) with U73122 (10 μM). Furthermore, this action of Ang II was completely abolished by co-inhibition of protein kinase C (PKC) and calcium/calmodulin protein kinase II (CaMKII). These results demonstrate that Ang II produces an inhibition of I Kv in CATH.a cells, via an intracellular pathway that includes PLC, PKC, and CaMKII.