K⁺-stimulation of the phosphoinositide pathway in guinea-pig ileum longitudinal smooth muscle is predominantly neuronal in origin and mediated by the entry of extracellular Ca²⁺

K⁺ and scorpion toxin stimulate formation of inositol phosphates in guinea-pig ileum longitudinal smooth muscle slices. The response to these two agents is not additive. The response to K⁺ is inhibited partially by nifedipine and partially by ω-conotoxin. When given together the effect of these two Ca²⁺ channel blockers is additive and the response of K⁺ is reduced by more than 80%. The response to scorpion toxin is inhibited completely by tetrodotoxin, partially by ω-conotoxin but not by atropine or nifedipine. Scorpion toxin induces a similar formation of inositol phosphates in collagenase-dispersed cells to that seen in cross-chopped slices. The responses to scorpion toxin and K⁺ are inhibited completely when the extracellular Ca²⁺ concentration is reduced to below cytosolic levels (<100 nM). Neither nifedipine nor ω-conotoxin, either alone or in combination, inhibited formation of inositol phosphates by substance P or carbachol. Both of these agonists induced a significant formation of inositol phosphates even when the extracellular Ca²⁺ concentration was reduced to 10 nM. These results indicate that K⁺ and scorpion toxin induce formation of inositol phosphates through the mobilisation of extracellular Ca²⁺. The response to K⁺ appears to occur predominantly in neuronal cells.