Membrane potential dependent modulations of calcium oscillations in insulin-secreting INS-1 cells
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AbstractThis study was undertaken to examine the role of K channels on cytosolic Ca(2+) ([Ca(2+)](i)) in insulin secreting cells. [Ca2+], was measured in single glucose-responsive INS-1 cells using the fluorescent Ca(2+) indicator Fura-2. Glucose, tolbutamide and forskolin elevated [Ca2+], and induced [Ca2] oscillations. Whereas the glucose effect was delayed and observed in 60% and 93% of the cells, in a poorly and a highly glucose-responsive INS-1 cell clone, respectively, tolbutamide and forskolin increased [Ca(2+)](i) in all cells tested. In the latter clone, glucose induced [Ca(2+)](i) oscillations in 77% of the cells. In 16% of the cells a sustained rise of [Ca(2+)](i) was observed. The increase in [Ca(2+)](i) was reversed by verapamil, an L-type Ca(2+) channel inhibitor. Adrenaline decreased [Ca(2+)](i) in oscillating cells in the presence of low glucose and in cells stimulated by glucose alone or in combination with tolbutamide and forskolin. Adrenaline did not lower [Ca(2+)](i) in the presence of 30 mM extracellular K(+), indicating that adrenaline does not exert a direct effect on Ca(2+) channels but increases K(+) channel activity. As for primary p-cells, [Ca(2+)](i) oscillations persisted in the presence of closed K(ATP) channels; these also persisted in the presence of thapsigargin, which blocks Ca(2+) uptake into Ca(2+) stores. In contrast, in voltage-clamped cells and in the presence of diazoxicle (50 muM), which hyperpolarizes the cells by opening K(ATP) channels, [Ca(2+)](i), oscillations were abolished. These results support the hypothesis that [Ca2+]i oscillations depend on functional voltage-dependent Ca(2+) and K(+) channels and are interrupted by a hyperpolarization in insulin-secreting cells. (C) 2002 Elsevier Science Ltd. All rights reserved.
All Author(s) ListHerbst M, Sasse P, Greger R, Huang Y, Hescheler J, Ullrich S
Journal nameCell Calcium
Volume Number31
Issue Number3
Pages115 - 126
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesCell Biology; CELL BIOLOGY

Last updated on 2020-20-10 at 02:43