guanosine-diphosphate and indo-1

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 ICa (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-beta-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. IBa from cell-attached patches was reduced by bath-applied angioII (mean 33%), suggesting use of a diffusible cytoplasmic messenger. M currents were inhibited by angioII in 8 of 11 neurons (mean 50%) cultured overnight. Hence, a second agonist, angioII, may share the slow, second messenger-utilizing, pertussis toxin-insensitive signaling pathway used by muscarinic agonists.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Biphenyl Compounds; Calcium; Calcium Channels; Egtazic Acid; Ethylmaleimide; Fluorescent Dyes; GTP-Binding Proteins; Guanosine Diphosphate; Imidazoles; In Vitro Techniques; Indoles; Ion Channels; Kinetics; Losartan; Membrane Potentials; Microscopy, Fluorescence; Neurons; Pertussis Toxin; Rats; Rats, Sprague-Dawley; Second Messenger Systems; Signal Transduction; Somatostatin; Superior Cervical Ganglion; Tetrazoles; Thionucleotides; Virulence Factors, Bordetella