Multiple actions of nitric oxide on voltage-dependent Ca2+ channels in mouse cerebral cortical neurons

Brain Res Mol Brain Res. 1998 Feb;54(1):133-40. doi: 10.1016/s0169-328x(97)00331-8.

Abstract

We investigated the effects of nitric oxide (NO) on voltage-dependent Ca2+ channels (VDCCs) by examining [45Ca2+]influx into mouse cerebral cortical neurons. S-nitroso-N-acetylpenicillamine (SNAP) induced a dose-dependent increase in [45Ca2+]influx, which was completely abolished by hemoglobin, tetrodotoxin and dibucaine. The NO-induced [45Ca2+influx was significantly inhibited by verapamil and omega-agatoxin VIA (omega-AGX), whereas omega-conotoxin GVIA (omega-CTX) had no effects on the NO-induced [45Ca2+]influx. KCl (30 mM) stimulated [45Ca2+]influx, and verapamil, omega-CTX and omega-AGX reduced the KCl-induced [45Ca2+]influx by about 40, 26 and 34%, respectively, indicating that the neurons used here possess L-, N- and P-typed VDCCs. SNAP itself reduced KCl-induced [45Ca2+]influx by about 28.5%. In the presence of both KCl and SNAP, omega-CTX showed no effects on the influx, while verapamil and omega-AGX significantly inhibited the influx and the concomitant presence of verapamil and omega-AGX completely abolished the influx. These results indicate that NO induces [45Ca2+] influx via the opening of L- and P-typed VDCCs subsequent to neuronal membrane depolarization and that NO itself inhibited the function of N-typed VDCC in the cerebral cortical neurons.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Calcium Radioisotopes
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism*
  • Fetus
  • Ion Channel Gating / drug effects*
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nitric Oxide / pharmacology*
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Potassium Chloride / pharmacology
  • S-Nitroso-N-Acetylpenicillamine

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Radioisotopes
  • Nitric Oxide
  • Potassium Chloride
  • S-Nitroso-N-Acetylpenicillamine
  • Penicillamine
  • Calcium