B. Buzas et al., CA2+ CALMODULIN-DEPENDENT TRANSCRIPTIONAL ACTIVATION OF DELTA-OPIOID RECEPTOR GENE-EXPRESSION INDUCED BY MEMBRANE DEPOLARIZATION IN NG108-15 CELLS/, Journal of neurochemistry, 70(1), 1998, pp. 105-112
Regulation of gene expression is one of the mechanisms by which neuron
al activity elicits long-term changes in neuronal phenotype and functi
on. Although activity-dependent induction of immediate-early genes has
been extensively studied, much less is known about the late-response
genes. We have investigated the activity-dependent regulation of delta
-opioid receptor (DOR) mRNA levels in NG108-15 cells. Transsynaptic ac
tivation was mimicked by depolarization with 55 mM KCl or veratridine.
Both treatments lead to a time-dependent increase of DOR mRNA levels.
Ca2+ entry through L-type voltage-dependent Ca2+ channels activated b
y depolarization appears to be involved, because L-type channel blocke
rs reduced the induction of DOR expression. Ca2+ binding to calmodulin
is the next step in the signal transduction pathway, because a calmod
ulin antagonist, W7, reduced the effect of veratridine. A selective in
hibitor of calmodulin kinases (KN-62) and cyclosporin, an inhibitor of
calcineurin, also antagonized the depolarization-induced increase in
DOR mRNA levels, which indicates that both calcium/calmodulin-dependen
t enzymes are involved in the activity-dependent induction of DOR gene
expression. induction of DOR gene expression by an activity-dependent
increase in intracellular Ca2+ concentration may serve as a feedback
regulatory mechanism because activation of DOR leads to hyperpolarizat
ion and lower excitability of neurons.