Submitted on October 17, 2005
Accepted on June 22, 2006
Involvement of stretch-activated cation channels in hypotonically induced insulin secretion in rat pancreatic 
-cells
Miki Takii1, Tomohisa Ishikawa2*, Hidetaka Tsuda1, Kazumitsu Kanatani1, Takaaki Sunouchi1, Yukiko Kaneko1, and Koichi Nakayama1
1 Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka, Japan
2 Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka, Japan; Shizuoka City, Shizuoka, Japan
* To whom correspondence should be addressed. E-mail: ishikat{at}u-shizuoka-ken.ac.jp.
In isolated rat pancreatic 
-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-aminoethoxydiphenyl borate, and ruthenium red, all cation channel blockers. In contrast, the ([Ca2+]c) elevation was not inhibited by suramine, a P2 purinoceptor antagonist. Whole-cell patch clamp analyses showed that hypotonic stimulation induced membrane depolarization of -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. Taken together, these results suggest that osmotic cell swelling activates cation channels in rat pancreatic -cells, thereby causing membrane depolarization and subsequent activation of voltage-dependent Ca2+ channels, thus elevating insulin secretion.
