Involvement of stretch-activated cation channels in hypotonically induced insulin secretion in rat pancreatic β-cells

In isolated rat pancreatic beta-cells, hypotonic stimulation elicited an increase in cytosolic Ca2+ concentration ([Ca2+](c)) at 2.8 mM glucose. The hypotonically induced [Ca-2+](c) elevation was significantly suppressed by nicardipine, a voltage- dependent Ca2+ channel blocker, and by Gd3+, amiloride, 2-aminoethoxydiphenylborate, and ruthenium red, all cation channel blockers. In contrast, the [Ca2+](c) elevation was not inhibited by suramin, a P-2 purinoceptor antagonist. Whole cell patch-clamp analyses showed that hypotonic stimulation induced membrane depolarization of beta-cells and produced outwardly rectifying cation currents; Gd3+ inhibited both responses. Hypotonic stimulation also increased insulin secretion from isolated rat islets, and Gd3+ significantly suppressed this secretion. Together, these results suggest that osmotic cell swelling activates cation channels in rat pancreatic beta-cells, thereby causing membrane depolarization and subsequent activation of voltage- dependent Ca2+ channels and thus elevating insulin secretion.