Potassium depolarisation markedly enhances muscarinic receptor stimulated inositol tetrakisphosphate accumulation in rat cerebral cortical slices.

Rat cerebral cortical slices labelled with [3H]-inositol were incubated with the muscarinic agonist carbachol in media containing normal 5.9 mM or elevated 24 mM K+ ions. Over the first few minutes both carbachol and elevated K+ stimulated the production of [3H]-inositol phosphates. The very rapid formation of [3H]-inositol tetrakis, tris and bisphosphate was followed by accumulation of [3H]-inositol monophosphate. However, elevated K+ resulted in a relatively larger stimulation of [3H]-inositol bisphosphate than muscarinic receptor stimulation. When carbachol effects were examined in media containing elevated K+, production of [3H]-inositol trisphosphate was apparently additive whereas the mono and bisphosphate displayed somewhat synergistic responses after 1-2 minutes. In contrast, [3H]-inositol tetrakisphosphate production was greatly enhanced and marked synergy was observed between the K+ and carbachol responses. The production of the tetrakisphosphate under these conditions was dependent on extracellular Ca2+ and a stimulatory effect of this divalent ion on the 3-kinase is discussed.