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Activation of Ca2+-Dependent K+ Channels Contributes to Rhythmic Firing of Action Potentials in Mouse Pancreatic β Cells
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We have applied the perforated patch whole-cell technique to β cells within intact pancreatic islets to identify the current underlying the glucose-induced rhythmic firing of action potentials. Trains of depolarizations (to simulate glucose-induced electrical activity) resulted in the gradual (time constant: 2.3 s) development of a small (<0.8 nS) K+ conductance. The current was dependent on Ca2+ influx but unaffected by apamin and charybdotoxin, two blockers of Ca2+-activated K+ channels, and was insensitive to tolbutamide (a blocker of ATP-regulated K+ channels) but partially (>60%) blocked by high (10–20 mM) concentrations of tetraethylammonium. Upon cessation of electrical stimulation, the current deactivated exponentially with a time constant of 6.5 s. This is similar to the interval between two successive bursts of action potentials. We propose that this Ca2+-activated K+ current plays an important role in the generation of oscillatory electrical activity in the β cell.
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“The existence of a KATP channel-independent component of Kslow (contributed by SK channels) might explain the paradox that slow waves persist in islets of SUR1 knockout mice, which lack functional KATP channels (157, 223).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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“The reduced exocytotic capacity of β-cells in intact islets is likewise not the consequence of reduced Ca2+ entry: if anything, the Ca2+ channel density is greater in β-cells in intact islets (223).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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“It is also blocked by TEA with an IC50 of ~5 mM (223) and by UCL1684.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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“Thus Kslow likely contributes to the pacemaker current.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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“which may account for the loss of normal oscillatory electrical activity seen in this preparation (but see (217)).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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“It has been reported that Kslow is reduced in dispersed β-cells maintained in tissue culture (223) which may account for the loss of normal oscillatory electrical activity seen in this preparation (but see (217)).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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“An early report that apamin is without effect on either glucose-induced electrical activity (374) or the amplitude of the Kslow current (12, 223) was therefore surprising (although see (669)).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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“The time and voltage-dependence of activation of Kslow echoes the changes in [Ca2+]i associated with (simulated) electrical activity (223).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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“Following cessation of electrical activity, the current deactivates with a time course similar to the slow depolarization between two successive bursts of action potentials (223).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [223]
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Citations
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Research works printed but not linked: 2
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Metadata
- Authors
- Göpel, S. O., Kanno, T., Barg, S., Eliasson, L., Galvanovskis, J., Renström, E., & Rorsman, P.
- Affiliations
- Lund University (SE)
- Venue
- The Journal of General Physiology
- Publisher
- Rockefeller University Press
- Published
- 1999-11-15
- Volume
- 114
- Issue
- 6
- Pages
- 759-770
- ISSN
- 0022-1295 (ISSN-L)
- 1540-7748
- PMC
- PMC2230648
- OpenAlex
- W2065171939
- Cited by
- 137
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 7 · 2014: 10 · 2013: 7 · 2012: 5
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of General Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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
- calcium-activated potassium channels, pancreatic beta cells, pancreatic islets, tetraethylammonium, ATP-sensitive potassium channels, apamin, charybdotoxin, tolbutamide, potassium conductance, bursting oscillations
- MeSH terms
- Action Potentials, Animals, Electrophysiology, Hypoglycemic Agents, Islets of Langerhans, Membrane Potentials, Tolbutamide, Potassium Channels, Patch-Clamp Techniques, ATP-Binding Cassette Transporters, Potassium Channels, Inwardly Rectifying, Potassium Channels, Calcium-Activated, Potassium Channel Blockers, Large-Conductance Calcium-Activated Potassium Channels, Mice, KATP Channels, In Vitro Techniques
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