| 14872319 |
Dufer M, Haspel D, Krippeit-Drews P, Aguilar-Bryan L, Bryan J, Drews G: Oscillations of membrane potential and cytosolic Ca (2+) concentration in SUR1 (-/-) beta cells. Diabetologia. 2004 Mar;47(3):488-98. Epub 2004 Feb 11.
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 Ca (2+) concentrations ([Ca (2+)](c)) and mitochondrial membrane potential (DeltaPsi) 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 Ca (2+)-dependent action potentials were detected. [Ca (2+)](c) showed various patterns of oscillations or a sustained increase. Sodium azide did not hyperpolarize SUR1 (-/-) beta cells. The depolarization of DeltaPsi evoked by sodium azide was significantly lower in SUR1 (-/-) than SUR1 (+/+) cells. Galanin transiently decreased action potential frequency and [Ca (2+)](c) in cells from both SUR1 (-/-) and SUR1 (+/+) mice. CONCLUSION/INTERPRETATION: The strong dependence of Vm and [Ca (2+)](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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