Acid secretagogues induce Ca2+ mobilization coupled to K+ conductance activation in rat parietal cells in tissue culture

Intracellular recordings from cultured parietal cells of the rat gastric fundus showed that carbachol, pentagastrin, histamine (in the presence of isobutylmethylxanthine; IBMX) and dibutyryl cyclic AMP induced hyperpolarizing responses which were sensitive to a K+ channel blocker, quinine. The Ca2+ ionophore, ionomycin, also induced a quinine-sensitive hyperpolarization. Deprivation of extracellular Ca2+ preferentially inhibited the hyperpolarizing responses to histamine (plus IBMX) and to dibutyryl cyclic AMP. Caffeine, oxalate and dantrolene sodium, which are known to affect Ca2+ transport in the endoplasmic reticulum, selectively inhibited the carbachol response. Mitochondrial inhibitors (KCN and carbonylcyanide p-trifluoromethoxyphenylhydrazone) preferentially suppressed the gastrin response. Cytosolic Ca2+ measurements with fura-2 indicated that significant increases in the intracellular concentration of free Ca2+ were induced not only by Ca2+-mediated acid secretagogues (carbachol and gastrin), but also by a cyclic AMP-mediated secretagogue (histamine plus IBMX). Dibutyryl cyclic AMP also increased cytosolic Ca2+ ions. It is concluded that stimulation of receptors to histamine, carbachol and gastrin gives rise to mobilization of Ca2+ ions into the cytoplasm from the different sources, thereby stimulating Ca2+-activated K+ channels in cultured rat parietal cells.