ANG II AT1 receptors induce depolarization and inward current in rat median preoptic neurons in vitro

To examine ANG II receptors in rat median preoptic (MnPO) neurons, we used patch-clamp whole cell recordings in a parasagittal brain slice preparation. Lucifer yellow-filled neurons displayed a simple morphology with two to three aspiny dendrites. Bath-applied ANG II (1-2,000 nM for 30 s) induced a response in 37 of 70 cells. In current-clamp recordings, cells displayed a prolonged (10- to 30-min) depolarizing plateau with action potential discharges and an associated reduction in postburst afterhyperpolarization and spike frequency adaptation. In voltage-clamp recordings (holding potential -65 mV), cells displayed tetrodotoxin-resistant inward currents of 7.6 +/- 1.9 (n = 5), 9.9 +/- 1.9 (n = 9), and 9.2 +/- 2.2 pA (n = 6) at 10,200, and 2,000 nM, respectively. Responses were blockable by pretreatment with losartan (2 mu M; n = 6) but not by PD-123177 (20 mu M; n = 3). Net ANG II-induced current revealed a 7.8 +/- 0.9% reduction in membrane conductance, decreasing but not reversing at hyperpolarized levels. Neurons expressing a strong hyperpolarization-activated, time-independent inward rectification were more likely to respond to ANG II. There was no correlation between the response of a neuron to ANG II and its response to norepinephrine.