Involvement of stretch-activated cation channels in hypotonically induced insulin secretion in rat pancreatic beta-cells.
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.
Takii
Miki
M
Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka, Japan.
Ishikawa
Tomohisa
T
Tsuda
Hidetaka
H
Kanatani
Kazumitsu
K
Sunouchi
Takaaki
T
Kaneko
Yukiko
Y
Nakayama
Koichi
K
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
D002412:Cations; D007038:Hypotonic Solutions; D007328:Insulin; D007473:Ion Channels; D002118:Calcium