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Glucose‐dependent regulation of rhythmic action potential firing in pancreatic β‐cells by k ATP ‐channel modulation
Author(s) -
Kanno T.,
Rorsman P.,
Göpel S. O.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.031344
Subject(s) - thapsigargin , tolbutamide , biophysics , bursting , chemistry , endocrinology , serca , resting potential , membrane potential , medicine , conductance , endoplasmic reticulum , potassium channel , beta cell , pancreatic islets , insulin , atpase , biology , biochemistry , islet , neuroscience , physics , enzyme , condensed matter physics
The regulation of a K + current activating during oscillatory electrical activity ( I K,slow ) in an insulin‐releasing β‐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 m m 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 ≈50 %. Increasing glucose from 15 to 30 m m , which likewise converted oscillatory electrical activity into continuous action potential firing, reduced I K,slow by ≈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 μ m ) inhibited I K,slow by 25 % and abolished bursting electrical activity. We conclude that oscillatory glucose‐induced electrical activity in the β‐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.