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

Olof Larsson, Henrik Kindmark, Robert Bränström, Bertil Fredholm, Per Olof Berggren

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Abstract

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 (KATP 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, KATP channel activity decreased and action potentials ensued. After 2-3 min, despite continuous stimulation, action potentials subsided and openings of KATP 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 KATP channel activity during continuous glucose stimulation result in oscillations in electrical activity and [Ca2+]i.

Original languageEnglish (US)
Pages (from-to)5161-5165
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number10
DOIs
StatePublished - May 14 1996

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