title: Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons via G proteins.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Washington, Seattle 98195.
authors.forename: M S
authors.initials: MS
authors.lastname: Shapiro
authors.forename: L P
authors.initials: LP
authors.lastname: Wollmuth
authors.forename: B
authors.initials: B
authors.lastname: Hille
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005456:Fluorescent Dyes; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D019808:Losartan; D008564:Membrane Potentials / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology; D017783:Superior Cervical Ganglion / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D015220:Calcium Channels; D005456:Fluorescent Dyes; D007093:Imidazoles; D007211:Indoles; D007473:Ion Channels; D013777:Tetrazoles; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D006153:Guanosine Diphosphate; D013004:Somatostatin; D004533:Egtazic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D019808:Losartan; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C048960:indo-1; D005033:Ethylmaleimide; D002118:Calcium