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

• Published in: American Journal of Physiology: Cell Physiology 2006-12, Vol.291 (6), p.C1405-C1411
• Main Authors: Takii, Miki, Ishikawa, Tomohisa, Tsuda, Hidetaka, Kanatani, Kazumitsu, Sunouchi, Takaaki, Kaneko, Yukiko, Nakayama, Koichi
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Cations - metabolism; Cell Size; Cells, Cultured; Hypotonic Solutions - chemistry; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Ion Channels - metabolism; Male; Membrane Potentials - physiology; Patch-Clamp Techniques; Rats; Rats, Wistar; Stress, Mechanical
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00519.2005

Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka, Japan Submitted 17 October 2005 ; accepted in final form 22 June 2006 In isolated rat pancreatic -cells, hypotonic stimulation elicited an increase in cytosolic Ca 2+ concentration ([Ca 2+ ] c ) at 2.8 mM glucose. The hypotonically induced [Ca 2+ ] c elevation was significantly suppressed by nicardipine, a voltage-dependent Ca 2+ channel blocker, and by Gd 3+ , amiloride, 2-aminoethoxydiphenylborate, and ruthenium red, all cation channel blockers. In contrast, the [Ca 2+ ] 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 -cells and produced outwardly rectifying cation currents; Gd 3+ inhibited both responses. Hypotonic stimulation also increased insulin secretion from isolated rat islets, and Gd 3+ significantly suppressed this secretion. 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 Ca 2+ channels and thus elevating insulin secretion. calcium ion; swelling; patch-clamp; gadolinium Address for reprint requests and other correspondence: T. Ishikawa, Dept. of Cellular and Molecular Pharmacology, Graduate School of Pharmaceut. Sci., Univ. of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka City, Shizuoka 422-8526, Japan (e-mail: ishikat{at}u-shizuoka-ken.ac.jp )