EFFECT OF POTASSIUM-INDUCED DEPOLARIZATION AN SOMATOSTATIN GENE-EXPRESSION IN CULTURED FETAL-RAT CEREBROCORTICAL CELLS

The stimulatory effect of potassium depolarization upon somatostatin ( SS) mRNA levels in primary cultures of fetal cerebrocortical cells was analyzed. Depolarizing stimuli, such as 56 mM K+ exposure for 30 min, elicited an increase in immunoreactive somatostatin (IR-SS) release t o the media and decreased SS mRNA levels. These were increased when ex posure to depolarization stimuli was prolonged up to 3 or more hr. At this time, potassium (30 and 56 mM) acted as a secretagogue, stimulati ng SS secretion, but was also effective in stimulating SS mRNA levels, suggesting that SS secretion can be coupled to SS mRNA accumulation. These changes were inhibited by the Ca2+ channel antagonist verapamil. In contrast, Na+ channel blockade by TTX did not modify the 24 hr pot assium-induced increase in SS mRNA, although it partially abolished po tassium-induced SS secretion. Examination of the rate of disappearance of SS mRNA levels after inhibition of mRNA transcription by actinomyc in-D revealed that K+ stimulation of cerebrocortical cells stabilized the SS mRNA. These results suggest that the induction of SS mRNA expre ssion by K+ is dose dependent, and involves the modulation of ion chan nels. The time-course study confirmed that the K+-induced SS mRNA accu mulation is time dependent, chronic activation of the Ca2+ channels be ing necessary to stimulate SS gene expression. K+ stimulation may also increase the level of SS mRNA in cerebrocortical cells by reducing it s rate of degradation.