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.

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.

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.

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.