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

Abstract

In isolated rat pancreatic β-cells, hypotonic stimulation elicited an increase in cytosolic Ca2+ concentration ([Ca2+]c) at 2.8 mM glucose. The hypotonically induced [Ca2+]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 P2 purinoceptor antagonist. Whole cell patch-clamp analyses showed that hypotonic stimulation induced membrane depolarization of β-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 β-cells, thereby causing membrane depolarization and subsequent activation of voltage-dependent Ca2+ channels and thus elevating insulin secretion.