Glucose-dependent regulation of rhythmic action potential firing in pancreatic beta-cells by K(ATP)-channel modulation.

Journal article

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.

Authors: Kanno, T; Rorsman, P; Göpel, S

• Publication status: Published
• Journal: Journal of physiology
• Volume: 545
• Issue: Pt 2
• Pages: 501-507
• Publication date: 2002-12-01
• DOI: 10.1113/jphysiol.2002.031344
• EISSN: 1469-7793
• ISSN: 0022-3751
• Language: English
• Keywords: Islets of Langerhans; Electrophysiology; Action Potentials; KATP Channels; ATP-Binding Cassette Transporters; Animals; Tolbutamide; Membrane Potentials; Calcium; Enzyme Inhibitors; Mice; Hypoglycemic Agents; Potassium Channels, Inwardly Rectifying; Thapsigargin; Glucose; Potassium Channels; Calcium Channels