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 (angioll) 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 AT(1) receptor antagonist losartan, attenuated by inclusion of 2 mM CDP-B-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 angioll-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.