Cited by 135Ion channel regulation and functionPancreatic function and diabetesIon Transport and Channel Regulation

Properties of single potassium channels modulated by glucose in rat pancreatic beta‐cells.

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Ashcroft, F M, Ashcroft, S J, Harrison, D E·1988·The Journal of Physiology

Abstract

1. The patch clamp method has been used to examine the effect of glucose on single K+ channel currents recorded from cell‐attached patches on dissociated rat pancreatic beta‐cells. Patch pipettes contained a 140 mM‐K+ solution. 2. In glucose‐free solution three types of K+ channels were observed. Two of these, having conductances of around 50 pS (G‐channel) and 20 pS when the external K+ concentration, [K+]0, was 140 mM, were active at the resting potential of the cell. The G‐channel was observed in more patches and showed higher activity; it therefore appears to contribute the major fraction of the resting K+ permeability of the beta‐cell. At membrane potentials positive to about +20 mV a third type of K+ channel, having a mean conductance of 120 pS, was activated. The open probability of this channel was strongly voltage dependent and increased with depolarization. 3. The reversal potential of the G‐channel current was shifted 59 mV by a 10‐fold change in external K+ (Na+ substitution) indicating the channel is highly K+ selective. The single‐channel conductance varied with [K+]o as predicted from the Goldman‐Hodgkin‐Katz equation; at physiological [K+]o (5 mM‐K+) an inward conductance of around 10 pS is predicted. The amplitude of the single‐channel current showed a tendency to saturate with increasing [K+]o. 4. Single G‐channel currents show burst kinetics indicating at least two closed states. The open and closed (gap) times within the bursts were distributed exponentially with time constants of 2.5 ms (tau o) and 0.5 ms (tau c1) respectively at the resting potential of the cell. There was little change in tau c1 over the voltage range ‐40 to 60 mV (pipette potential) but tau o increased slightly with membrane depolarization. 5. The addition of glucose to the bath solution produced a reversible, dose‐dependent decrease in G‐channel activity. This decrease results principally from a reduction in the frequency and duration of the bursts of openings with increasing glucose. In addition, the mean open time decreases. The short gaps during the bursts were little affected by glucose. 6. At glucose concentrations of .10 mM and above the decrease in G‐channel activity is accompanied by an increase in the input resistance of the cell and by the initiation of action potentials. 7. It is concluded that glucose metabolism results in a reduction of G‐channel open probability and thereby produces depolarization of the beta‐cell.

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Crossref · 10.1113/jphysiol.1988.sp017134

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  • In both whole-cell and perforated-patch preparations, glucose produces a concentration-dependent reduction of whole-cell KATP conductance that is half-maximal at 3-4 mM glucose.

    “In both preparations, glucose produces a concentration-dependent reduction of the whole-cell conductance which, when expressed as a fraction of that in the absence of glucose, is half-maximal at 3-4 mM glucose (26, 212, 584, 674, 762).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [26]

    The paper’s numbered findings report a reversible, dose-dependent decrease in G-channel activity with glucose, accompanied by increased cell input resistance. But the experiments described use single-channel recordings from cell-attached patches; our copy does not establish the claimed result in both whole-cell and perforated-patch preparations or a half-maximal concentration of 3–4 mM. (LLM, conf=0.86)

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Research works printed but not linked: 50

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Cited by

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Authors
Ashcroft, F. M., Ashcroft, S. J., & Harrison, D. E.
Affiliations
University of Oxford (GB)
Venue
The Journal of Physiology
Publisher
Wiley
Published
1988-06
Volume
400
Issue
1
Pages
501-527
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
OpenAlex
W2032897738
Cited by
135
References
1
Citations by year
2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 2 · 2017: 3 · 2015: 1 · 2014: 4 · 2013: 6 · 2012: 2
FWCI
4.74
Type
journal article
Language
en
Open access
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
potassium channels, pancreatic beta cells, single-channel conductance, open probability, voltage dependence, burst kinetics, input resistance, action potential, glucose metabolism, Goldman-Hodgkin-Katz equation
MeSH terms
Action Potentials, Animals, Glucose, Insulin, Ion Channels, Islets of Langerhans, Kinetics, Male, Membrane Potentials, Potassium, Rats, Inbred Strains, Time Factors, Rats, In Vitro Techniques

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