Electrophysiology of pancreatic β-cells in intact mouse islets of Langerhans
Abstract
When exposed to intermediate glucose concentrations (6-16 mol/l), pancreatic β-cells in intact islets generate bursts of action potentials (superimposed on depolarised plateaux) separated by repolarised electrically silent intervals. First described more than 40 years ago, these oscillations have continued to intrigue β-cell electrophysiologists. To date, most studies of β-cell ion channels have been performed on isolated cells maintained in tissue culture (that do not burst). Here we will review the electrophysiological properties of β-cells in intact, freshly isolated, mouse pancreatic islets. We will consider the role of ATP-regulated K⁺-channels (K(ATP)-channels), small-conductance Ca²⁺-activated K⁺-channels and voltage-gated Ca²⁺-channels in the generation of the bursts. Our data indicate that K(ATP)-channels not only constitute the glucose-regulated resting conductance in the β-cell but also provide a variable K⁺-conductance that influence the duration of the bursts of action potentials and the silent intervals. We show that inactivation of the voltage-gated Ca²⁺-current is negligible at voltages corresponding to the plateau potential and consequently unlikely to play a major role in the termination of the burst. Finally, we propose a model for glucose-induced β-cell electrical activity based on observations made in intact pancreatic islets.
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At 10 mM glucose, the active and silent phases last 5-10 s and 10-20 s, respectively, with 2-4 bursts/min.
“At 10 mM glucose, the active and silent phases last 5-10 s and 10-20 s, respectively and there are 2-4 bursts/min (154, 273, 570).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [570]
Opening of voltage-gated Ca2+ channels plays a critical role in the upstroke of the β-cell action potential, and their blockade inhibits action potential firing and insulin secretion.
“Their opening plays a critical role in the upstroke of the β-cell action potential and their blockade leads to inhibition of action potential firing and insulin secretion (570).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [570]
The action potentials of both mouse and human β-cells are short, ranging between 5 ms (human) and 30-40 ms (mouse).
“The action potentials of both mouse and human β-cells are short, ranging between 5 ms (human) and 30-40 ms (mouse) (568, 570).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [570]
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“This is in agreement with investigations of Ca current recovery in mouse beta-cells [40].”
Self-citationMultilevel synchronization of human β-cells networks
Luchetti, N., Filippi, S., & Loppini, A. (2023) · Frontiers in Network Physiology · doi:10.3389/fnetp.2023.1264395 · Cited by 3 · see citing works
“Endocrine β -cells activity is crucial for regulating blood glucose levels, as well as lipid and protein metabolism, through coordinated bursting oscillations triggering a calcium-driven insulin release (Dimitriadis et al., 2011; Rorsman et al., 2011; Rorsman and Braun, 2013).”
Improving the physiological realism of experimental models
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“In mouse beta-cells, the glucose-induced electrical activity (that emerges at glucose concentrations 6–7 mM) is oscillatory and consists of depolarized plateaux on which action potentials are superimposed that are separated by repolarized and electrically silent intervals [41,42].”
BackgroundSelf-citation5,7-dihydroxy-3,4,6-trimethoxyflavone attenuates ischemic damage and apoptosis in mouse islets.
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Ion Channels and Regulation of Insulin Secretion in Beta-Cells
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STIM1 regulates pancreatic β-cell behaviour: A modelling study
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Redox Signaling is Essential for Insulin Secretion
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SWELL1 is a glucose sensor required for β-cell excitability and insulin secretion
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- Authors
- Rorsman, P., Eliasson, L., Kanno, T., Zhang, Q., & Gopel, S.
- Affiliations
- University of Alberta (CA)
- Lund University (SE)
- Fukushima Medical University (JP)
- Corresponding author
- Rorsman, Patrik
- Venue
- Progress in Biophysics and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 107
- Issue
- 2
- Pages
- 224-235
- ISSN
- 0079-6107 (ISSN-L)
- OpenAlex
- W2022680688
- Cited by
- 103
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 10 · 2020: 3 · 2019: 5 · 2018: 11 · 2017: 9 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 8 · 2012: 10
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Biophysics and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Wellcome Trust (095531/Z/11/Z, 095531)
- Diabetes UK
- Canada Research Chairs
- Medical Research Council
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- pancreatic beta cells, pancreatic islets, burst firing, glucose regulation, small conductance Ca2+-activated K+ channels, silent intervals, plateau potentials, mice
- MeSH terms
- Animals, Cations, Glucose, Humans, Insulin-Secreting Cells, Mice, KATP Channels, Electrophysiological Phenomena
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