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

J Physiol. 2002 Dec 1;545(2):501-7. doi: 10.1113/jphysiol.2002.031344.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • ATP-Binding Cassette Transporters
  • Calcium Channels
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • KATP Channels
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • uK-ATP-1 potassium channel
  • Thapsigargin
  • Tolbutamide
  • Glucose
  • Calcium