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

Neuron. 1994 Jun;12(6):1319-29. doi: 10.1016/0896-6273(94)90447-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / pharmacology*
  • Angiotensin Receptor Antagonists
  • Animals
  • Biphenyl Compounds / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Ethylmaleimide / pharmacology
  • Fluorescent Dyes
  • GTP-Binding Proteins / metabolism*
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / pharmacology
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Indoles
  • Ion Channels / drug effects
  • Ion Channels / physiology*
  • Kinetics
  • Losartan
  • Membrane Potentials / drug effects
  • Microscopy, Fluorescence
  • Neurons / drug effects
  • Neurons / physiology*
  • Pertussis Toxin
  • Rats
  • Rats, Sprague-Dawley
  • Second Messenger Systems
  • Signal Transduction / drug effects
  • Somatostatin / pharmacology
  • Superior Cervical Ganglion / physiology*
  • Tetrazoles / pharmacology
  • Thionucleotides / pharmacology
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Calcium Channels
  • Fluorescent Dyes
  • Imidazoles
  • Indoles
  • Ion Channels
  • Tetrazoles
  • Thionucleotides
  • Virulence Factors, Bordetella
  • Angiotensin II
  • Guanosine Diphosphate
  • Somatostatin
  • Egtazic Acid
  • guanosine 5'-O-(2-thiodiphosphate)
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Losartan
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • indo-1
  • Ethylmaleimide
  • Calcium