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

Kanno, T; Rorsman, Patrik LU and Göpel, Sven LU (2002) In Journal of Physiology 545(2). p.501-507
Abstract
The regulation of a K+ current activating during oscillatory electrical activity (I-K,I-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 IK,slow by similar to50%. Increasing glucose from 15 to 30 mm, which likewise converted oscillatory electrical activity into continuous action potential firing, reduced I-K,I-slow by similar to30% whilst not affecting the resting conductance. Action... (More)
The regulation of a K+ current activating during oscillatory electrical activity (I-K,I-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 IK,slow by similar to50%. Increasing glucose from 15 to 30 mm, which likewise converted oscillatory electrical activity into continuous action potential firing, reduced I-K,I-slow by similar to30% whilst not affecting the resting conductance. Action potential firing may culminate in opening of K-ATP channels by activation of ATP-dependent Ca2+ pumping as suggested by the observation that the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor thapsigargin (4 muM) inhibited I-K,I-slow by 25% and abolished bursting electrical activity. We conclude that oscillatory glucose-induced electrical activity in the beta-cell involves the opening of KATP-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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Physiology
volume
545
issue
2
pages
501 - 507
publisher
The Physiological Society
external identifiers
  • pmid:12456829
  • wos:000180075200018
  • scopus:0036905897
ISSN
1469-7793
DOI
10.1113/jphysiol.2002.031344
language
English
LU publication?
yes
id
bac401d5-1fa3-4bae-82e6-296b864b68e2 (old id 320611)
date added to LUP
2007-11-02 10:40:48
date last changed
2017-10-08 04:26:41
@article{bac401d5-1fa3-4bae-82e6-296b864b68e2,
  abstract     = {The regulation of a K+ current activating during oscillatory electrical activity (I-K,I-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 IK,slow by similar to50%. Increasing glucose from 15 to 30 mm, which likewise converted oscillatory electrical activity into continuous action potential firing, reduced I-K,I-slow by similar to30% whilst not affecting the resting conductance. Action potential firing may culminate in opening of K-ATP channels by activation of ATP-dependent Ca2+ pumping as suggested by the observation that the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor thapsigargin (4 muM) inhibited I-K,I-slow by 25% and abolished bursting electrical activity. We conclude that oscillatory glucose-induced electrical activity in the beta-cell involves the opening of KATP-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.},
  author       = {Kanno, T and Rorsman, Patrik and Göpel, Sven},
  issn         = {1469-7793},
  language     = {eng},
  number       = {2},
  pages        = {501--507},
  publisher    = {The Physiological Society},
  series       = {Journal of Physiology},
  title        = {Glucose-dependent regulation of rhythmic action potential firing in pancreatic beta-cells by K-ATP-channel modulation},
  url          = {http://dx.doi.org/10.1113/jphysiol.2002.031344},
  volume       = {545},
  year         = {2002},
}