The stimulatory effect of potassium depolarization upon somatostatin mRNA (SS mRNA) levels in primary cultures of fetal cerebrocortical cells was analyzed. Depolarizing stimuli, such as 56 mM K+ concentration for 24 hours, elicited an increase in immunoreactive somatostatin (IR-SS) release to the media and SS mRNA levels, suggesting that somatostatin secretion can be coupled to SS mRNA accumulation. These changes were inhibited by the Ca2+ channel antagonist verapamil (VPM). In contrast, Na+ channel blockade by tetrodotoxin (TTX) did not modify the 24 h potassium-induced increase in SS mRNA. These results suggest that the induction of SS mRNA expression by K+ involves the modulation of calcium ion channels.