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The regulation of a K(+) current activating during oscillatory electrical activity (I(K,slow)) in an insulin-releasing beta-cell was studied by applying the perforated patch whole-cell technique to intact mouse pancreatic islets. The resting whole-cell conductance in the presence of 10 mM glucose amounted to 1.3 nS, which rose by 50 % during a series of 26 simulated action potentials. Application of the K(ATP)-channel blocker tolbutamide produced uninterrupted action potential firing and reduced I(K,slow) by approximately 50 %. Increasing glucose from 15 to 30 mM, which likewise converted oscillatory electrical activity into continuous action potential firing, reduced I(K,slow) by approximately 30 % whilst not affecting the resting conductance. Action potential firing may culminate in opening of K(ATP) channels by activation of ATP-dependent Ca(2+) pumping as suggested by the observation that the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin (4 microM) inhibited I(K,slow) by 25 % and abolished bursting electrical activity. We conclude that oscillatory glucose-induced electrical activity in the beta-cell involves the opening of K(ATP)-channel activity and that these channels, in addition to constituting the glucose-regulated K(+) conductance, also play a role in the graded response to supra-threshold glucose concentrations.

Type

Journal article

Journal

J Physiol

Publication Date

01/12/2002

Volume

545

Pages

501 - 507

Keywords

ATP-Binding Cassette Transporters, Action Potentials, Animals, Calcium, Calcium Channels, Electrophysiology, Enzyme Inhibitors, Glucose, Hypoglycemic Agents, In Vitro Techniques, Islets of Langerhans, KATP Channels, Membrane Potentials, Mice, Potassium Channels, Potassium Channels, Inwardly Rectifying, Thapsigargin, Tolbutamide