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-P4 in rat brain cortical slices was maximal in buffer containing 10 mM K+. Iso-osmotic elevation of extracellular K+ to 30 mM did not affect total Ins 1,3,4,5-P4 accumulation but did enhance carbachol stimulated Ins 1,4,5-P3 accumulation. Iso-osmotically elevated K+ suppressed carbachol stimulated accumulation of labeled IP4 while enhancing accumulation of labeled inositol mono-, bis- and trisphosphates. High K+ alone increased basal accumulation of labeled inositol mono-, bis- and trisphosphates, and total Ins 1,4,5-P3, while having no significant effect on accumulation of labeled IP4 or total Ins 1,3,4,5-P4. Long-term incubation with hyper-osmotically elevated K+ potentiated carbachol-stimulated Ins 1,3,4,5-P4 accumulation at 5 min. However, hyper-osmotically elevated K+ suppressed accumulation of labeled IP4 due to carbachol. These results indicate that there is no short-term effect of iso-osmotically elevated K+ on carbachol-stimulated total Ins 1,3,4,5-P4 accumulation. Furthermore, elevating K+ above 10 mM either iso-osmotically or hyper-osmotically suppresses carbachol stimulated accumulation of labeled IP4. The results suggest that the altered Na+/K+ ratio influenced the production of inositol tetrakisphosphates and emphasize the important role of cations such as Na+, K+, and Ca2+ in the receptor-mediated inositol response. Moreover, the results underscore the unique ability of carbachol (a cholinergic agonist) to stimulate significant accumulation of inositol tetrakisphosphate.