Angiotensin II type 2 receptor-mediated regulation of rat neuronal K+ channels

We have previously shown that angiotensin II (Ang II), via AT(2) receptors, increases whole-cell K+ current in cultured rat hypothalamus and brain stem neurons. We have now investigated the AT(2) receptor-mediated effects of Ang II on the activity of single delayed rectifier K+ channels in cell-attached membrane patches. In control recordings (bath, 5.4 mmol/L K+; pipette, 140 mmol/L K+), two voltage-dependent channels were recorded with conductances of 34+/-4 and 56+/-6 pS, respectively (n=6). When patches were excised, the channels reversed near a membrane potential expected for a K+ channel. In cell-attached patches (-40 mV), Ang IT (100 nmol/L) increased open probability of the 56-pS K+ channel from 0.03+/-0.01 to 0.21+/-0.05 (n=3). The selective AT(2) receptor antagonist PD 123319 (1 mu mol/L) but not the AT(1) receptor antagonist losartan (1 mu mol/L) blocked the actions of Ang II (n=3). The selective AT(2) receptor agonist CGP 42112 (100 nmol/L) produced similar effects to Ang II. Kinetic analysis of the Ang II effect showed that open-time histograms were best fit by two exponential functions. Ang II increased both open-time constants relative to control (control, tau(1)=0.9+/-0.1 milliseconds, tau(2)=2.3+/-0.3 milliseconds; Ang II, tau(1)=3.1+/-0.4 milliseconds, tau(2)=12.1+/-2.4 milliseconds), and PD 123319 blocked this effect (n=3). The closed-time histogram was not affected by Ang II, PD 123319, or losartan. These results suggest that activation of AT(2) receptors modulates rat hypothalamus and brain stem neuronal whole-cell K+ current by increasing the open probability of a 56-pS K+ channel.