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Journal of Neuroscience, Vol 12, 2973-2981, Copyright © 1992 by Society for Neuroscience
NMDA and non-NMDA receptor-mediated increase of c-fos mRNA in dentate gyrus neurons involves calcium influx via different routes
LS Lerea, LS Butler and JO McNamara
Department of Medicine, Veterans Administration Medical Center, Durham, North Carolina.
We examined the effects of selective agonists of ionotropic excitatory
amino acid (EAA) receptor subtypes on induction of the immediate early gene
c-fos. We used in situ hybridization to measure c-fos mRNA and fura-2
imaging to measure intracellular calcium (Ca2+i) in individual dentate
gyrus neurons maintained in vitro. Activation of either NMDA or non-NMDA
receptor subtypes is sufficient to induce the rapid and dramatic increase
of c-fos mRNA. Activation of either NMDA or non-NMDA receptors also induces
a rapid and dramatic increase of Ca2+i, effects blocked by the removal or
chelation of extracellular calcium (Ca2+e). c- fos mRNA induction by either
receptor subtype is Ca2+ dependent, since chelation of Ca2+e with EGTA
prevents c-fos mRNA induction by both NMDA and non-NMDA receptor agonists.
The increase in Ca2+i induced by activating non-NMDA receptors is inhibited
either by removal of extracellular sodium (Na+e) or by the
voltage-sensitive calcium channel (VSCC) blocker nifedipine. By contrast,
the increase of Ca2+i induced by activating NMDA receptors is not inhibited
by removal of Na+e or nifedipine. Consistent with these effects on Ca2+i,
nifedipine inhibits induction of c-fos mRNA by non-NMDA, but not by NMDA,
receptor agonists. These findings indicate that Ca2+ serves as a second
messenger coupling ionotropic EAA receptors with transcriptional activation
of c-fos mRNA. The route of Ca2+ entry into dentate neurons, however,
depends on the EAA receptor subtype stimulated. Non-NMDA receptor
activation results in Ca2+ influx indirectly via VSCCs, whereas NMDA
receptor activation results in Ca2+ influx directly through the NMDA
channel itself.(ABSTRACT TRUNCATED AT 250 WORDS)
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