Potassium depolarization-induced cAMP stimulates somatostatin mRNA levels in cultured diencephalic neurons

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.