Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons via G proteins

We characterized inhibition of N-type Ca²⁺ and M current K⁺ channels in rat superior cervical ganglion neurons by angiotensin II (angioII) using the patch clamp. Of 120 neurons, 97 showed inhibition of I_Ca (mean 32%), which was slow in onset and very slow to reverse under whole-cell recording conditions. This inhibition was blocked by the AT₁ receptor antagonist losartan, attenuated by inclusion of 2 mM GDP-β-S in the pipette, mostly pertussis toxin insensitive, half-sensitive to N-ethylmaleimide, and wholly voltage independent. With 20 mM instead of 0.1 mM BAPTA in the pipette, the inhibition was strongly attenuated; however, we detected no angioII-induced [Ca²⁺]_i signal using the fluorescent indicator indo-1. I_Ba from cell-attached patches was reduced by bath-applied angioll (mean 33%), suggesting use of a diffusible cytoplasmic messenger. M currents were inhibited by angioll in 8 of 11 neurons (mean 50%) cultured overnight. Hence, a second agonist, angioll, may share the slow, second messenger-utilizing, pertussis toxin-insensitive signaling pathway used by muscarinic agonists.