Oscillations in K_ATP channel activity promote oscillations in cytoplasmic free Ca²⁺ concentration in the pancreatic β cell

Pancreatic β cells exhibit oscillations in electrical activity, cytoplasmic free Ca²⁺ concentration ([Ca²⁺]_i), and insulin release upon glucose stimulation. The mechanism by which these oscillations are generated is not known. Here we demonstrate fluctuations in the activity of the ATP-dependent K⁺ channels (K_ATP channels) in single β cells subject to glucose stimulation or to stimulation with low concentrations of tolbutamide. During stimulation with glucose or low concentrations of tolbutamide, K_ATP channel activity decreased and action potentials ensued. After 2-3 min, despite continuous stimulation, action potentials subsided and openings of K_ATP channels could again be observed. Transient suppression of metabolism by azide in glucose-stimulated β cells caused reversible termination of electrical activity, mimicking the spontaneous changes observed with continuous glucose stimulation. Thus, oscillations in K_ATP channel activity during continuous glucose stimulation result in oscillations in electrical activity and [Ca²⁺]_i.