Voltage-dependent calcium channel involvement in NMDA-induced activation of NOS.
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.
Alagarsamy
S
S
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Johnson
K M
KM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004789:Enzyme Activation; D005625:Frontal Lobe / Q000187:drug effects* / Q000201:enzymology; D007059:Ictaluridae; D015640:Ion Channel Gating; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000819:agonists*; D051381:Rats
D002121:Calcium Channel Blockers; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase