ANGIOTENSIN-II TYPE-2 RECEPTOR-MODULATED CHANGES IN POTASSIUM CURRENTS IN CULTURED NEURONS

We have previously shown that angiotensin II (ANG II) stimulates an in crease in net outward ionic current (I(no)) in neurons cocultured from neonate rat hypothalamus and brain stem, an effect mediated by ANG II type 2 (AT2) receptors. I(no) consists mainly of K+ and Ca2+ currents , and in the present study we used whole cell voltage clamp procedures to define which of these currents are modulated by AT2 receptors. We determined that ANG II (50-100 nM) stimulated both transient K+ curren t (I(A)) and delayed-rectifier K+ current (I(K)) in cultured neurons. The effects were mediated by AT2 receptors (blocked by 1 muM PD-123177 but not by 1 muM losartan). For both I(A) and I(K), ANG II elicited a n increase in maximal conductance. By contrast, ANG II altered neither Ca2+-activated K+ current nor Ca2+ current. Our data demonstrate disc rete AT2 receptor-mediated effects of ANG II on I(A) and I(K) in cultu red neonate neurons. Importantly, these data provide an electrophysiol ogical basis for behavioral or physiological effects (as yet undefined ) mediated by this ANG II receptor subtype in the brain.