EFFECT OF K-INDUCED DEPOLARIZATION ON CARBACHOL-STIMULATED INOSITOL TETRAKISPHOSPHATE ACCUMULATION IN RAT CEREBROCORTICAL SLICES()

Carbachol-stimulated accumulation of labeled IP4 or of total Ins 1,3,4 ,5-P-4 in rat brain cortical slices was maximal in buffer containing 1 0 mM K+. Iso-osmotic elevation of extracellular K+ to 30 mM did not af fect total Ins 1,3,4,5-P-4 accumulation but did enhance carbachol stim ulated Ins 1,4,5-P-3 accumulation. Iso-osmotically elevated K+ suppres sed carbachol stimulated accumulation of labeled IP4 while enhancing a ccumulation of labeled inositol mono-, bis- and trisphosphates. High K + alone increased basal accumulation of labeled inositol mono-, bis- a nd trisphosphates, and total Ins 1,4,5-P-3, while having no significan t effect on accumulation of labeled IP4 or total Ins 1,3,4,5-P-4. Long -term incubation with hyper-osmotically elevated K+ potentiated carbac hol-stimulated Ins 1,3,4,5-P-4 accumulation at 5 min. However, hyper-o smotically elevated K+ suppressed accumulation of labeled IP4 due to c arbachol. These results indicate that there is no short-term effect of iso-osmotically elevated K+ on carbachol-stimulated total Ins 1,3,4,5 -P-4 accumulation. Furthermore, elevating K+ above 10 mM either iso-os motically or hyper-osmotically suppresses carbachol stimulated accumul ation of labeled IP4. The results suggest that the altered Na+/K+ rati o influenced the production of inositol tetrakisphosphates and emphasi ze the important role of cations such as Na+, K+, and Ca2+ in the rece ptor-mediated inositol response. Moreover, the results underscore the unique ability of carbachol (a cholinergic agonist) to stimulate signi ficant accumulation of inositol tetrakisphosphate.