Voltage-dependent calcium channel involvement in NMDA-induced activation of NOS

Neuroreport. 1995 Nov 13;6(16):2250-4. doi: 10.1097/00001756-199511000-00035.


We have previously shown that N-methyl-D-aspartate (NMDA) increases nitric oxide synthase (NOS) activity in rat frontal cortex; however, the actual mechanism of this activation has not been addressed. Tetrodotoxin (TTX; 0.05 microM) inhibited NMDA-activated NOS, suggesting that TTX-sensitive Na+ channels are interposed between the NMDA receptors and the NOS cellular compartment. The NMDA response was also blocked by voltage-dependent Ca2+ channel (VDCC) blockers including Cd2+, Co2+, funnel web spider toxin (FTX) and omega-Aga IVa, but not by nifedipine or omega-conotoxin. These data suggest that Ca2+ flux through P- and/or Q-type VDCC subsequent to NMDA-induced depolarization may be at least as important for NOS activation as Ca2+ entry through the NMDA receptor.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Enzyme Activation
  • Frontal Lobe / drug effects*
  • Frontal Lobe / enzymology
  • Ictaluridae
  • Ion Channel Gating
  • N-Methylaspartate / antagonists & inhibitors
  • N-Methylaspartate / pharmacology*
  • Nitric Oxide Synthase / agonists*
  • Rats


  • Calcium Channel Blockers
  • N-Methylaspartate
  • Nitric Oxide Synthase