title: Involvement of stretch-activated cation channels in hypotonically induced insulin secretion in rat pancreatic beta-cells.
abstract: In isolated rat pancreatic beta-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 beta-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 beta-cells, thereby causing membrane depolarization and subsequent activation of voltage-dependent Ca(2+) channels and thus elevating insulin secretion.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Takii
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Tsuda
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Kanatani
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sunouchi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D007038:Hypotonic Solutions / Q000737:chemistry*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
chemical_list: D002412:Cations; D007038:Hypotonic Solutions; D007328:Insulin; D007473:Ion Channels; D002118:Calcium