In the nervous system, signals transmitted across synapses are known to reg
ulate gene expression in the postsynaptic cells. This process often involve
s membrane depolarization and subsequent elevation of intracellular Ca2+. W
e have previously demonstrated in fetal cerebrocortical cells, that somatos
tatin (SS) mRNA levels can be induced by depolarizing agents such as high p
otassium concentrations and veratridine (VTD), and that these effects are c
alcium dependent. SS expression is regulated by cAMP, and in the cerebral c
ortex adenylate cyclase activity is regulated through fluctuations in intra
cellular Ca2+ concentrations. The present experiments were undertaken to de
termine the mechanism by which calcium upregulates the levels of SS mRNA. C
erebrocortical cells from 17-day-old fetuses were exposed to the different
agents for 24 h and the levels of SS mRNA were measured by Northern blot. I
ncubation of cells with the calcium channel antagonist nifedipine (Nf), the
calcium chelating agent EGTA, calcium free KRB and the calcium calmodulin
inhibitors trifluoroperazine (TFP) and the napthelene sulfonamide, W7, resu
lted in the inhibition of K+-induced SS mRNA levels. K+-evoked depolarizati
on increased the intracellular concentration of cAMP and this effect was an
tagonized by verapamil (VPM). Forskolin (Fk) provoked a higher increment in
cAMP concentration than potassium, although the induction of SS mRNA was m
ore evident following K+ depolarization indicating a lack of correlation be
tween levels of cAMP and induction of SS mRNA. The role of K+-induced cAMP
on the increment of SS mRNA that occurred upon membrane depolarization was
further explored with the inhibitor of protein kinase A (PKA), Rp cAMP whos
e presence significantly reduced depolarization-induced SS mRNA levels. Thi
s study confirms that Ca2+ influx is required for K+ depolarization-induced
stimulation of cAMP whereby the increment of SS mRNA is partly produced. (
C) 2000 Elsevier Science B.V. All rights reserved.