Mobilization of different intracellular calcium pools after activation of muscarinic receptors in pancreatic beta-cells.

Exposure to carbachol resulted in a biphasic stimulation of 45Ca efflux when beta-cell-rich pancreatic islets from ob/ob mice were perifused with a Ca2+-deficient medium. The pattern of stimulated 45Ca efflux was markedly modified by glucose. Whereas the initial carbachol-stimulated phase was conditional on previous exposure to glucose, the subsequent phase was completely suppressed by 20 mmol/l of the sugar. The stimulatory could be clearly separated also on the basis of a Na+ dependence. Removal of extracellular Na+ resulted in a disappearance of the second phase, but it was still possible to induce a prominent initial peak if depletion of intracellular K+ was prevented when Na+ was omitted. It is concluded that activation of muscarinic receptors in the pancreatic beta-cells results in mobilization of calcium from more than one intracellular pool. Whereas the second phase of stimulated efflux can be explained in terms of an increased entry of Na+ into the beta-cells, the initial stimulation may be due to receptor-mediated breakdown of polyphosphoinositides.