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Diabetologia

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01-03-2004 | Article

Oscillations of membrane potential and cytosolic Ca²⁺ concentration in SUR1^−/− beta cells

Authors: M. Düfer, D. Haspel, P. Krippeit-Drews, L. Aguilar-Bryan, J. Bryan, G. Drews

Published in: Diabetologia | Issue 3/2004

Abstract

Aims/hypothesis

SUR1(ABCC8)^−/− mice lacking functional K_ATP channels are an appropriate model to test the significance of K_ATP channels in beta-cell function. We examined how this gene deletion interferes with stimulus-secretion coupling. We tested the influence of metabolic inhibition and galanin, whose mode of action is controversial.

Methods

Plasma membrane potential (Vm) and currents were measured with microelectrodes or the patch-clamp technique; cytosolic Ca²⁺ concentrations ([Ca²⁺]_c) and mitochondrial membrane potential (ΔΨ) were measured using fluorescent dyes.

Results

In contrast to the controls, SUR1^−/− beta cells showed electrical activity even at a low glucose concentration. Continuous spike activity was measured with the patch-clamp technique, but with microelectrodes slow oscillations in Vm consisting of bursts of Ca²⁺-dependent action potentials were detected. [Ca²⁺]_c showed various patterns of oscillations or a sustained increase. Sodium azide did not hyperpolarize SUR1^−/− beta cells. The depolarization of ΔΨ evoked by sodium azide was significantly lower in SUR1^−/− than SUR1^+/+ cells. Galanin transiently decreased action potential frequency and [Ca²⁺]_c in cells from both SUR1^−/− and SUR1^+/+ mice.

Conclusion/interpretation

The strong dependence of Vm and [Ca²⁺]_c on glucose concentration observed in SUR1^+/+ beta cells is disrupted in the knock-out cells. This demonstrates that both parameters oscillate in the absence of functional K_ATP channels. The lack of effect of metabolic inhibition by sodium azide shows that in SUR1^−/− beta cells changes in ATP/ADP no longer link glucose metabolism and Vm. The results with galanin suggest that this peptide affects beta cells independently of K_ATP currents and thus could contribute to the regulation of beta-cell function in SUR1^−/− animals.

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Title: Oscillations of membrane potential and cytosolic Ca2+ concentration in SUR1−/− beta cells
Authors: M. Düfer
D. Haspel
P. Krippeit-Drews
L. Aguilar-Bryan
J. Bryan
G. Drews
Publication date: 01-03-2004
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 3/2004
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-004-1348-0

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Abstract

Aims/hypothesis

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