BK channels mediate a novel ionic mechanism that regulates glucose-dependent electrical activity and insulin secretion in mouse pancreatic β-cells: BK channels in pancreatic beta cells
Open accessAbstract
BK channels are large unitary conductance K(+) channels cooperatively activated by intracellular calcium and membrane depolarisation. We show that BK channels regulate electrical activity in β-cells of mouse pancreatic islets exposed to elevated glucose. In 11.1 mM glucose, the non-peptidyl BK channel blocker paxilline increased the height of β-cell action potentials (APs) by 21 mV without affecting burst- or silent-period durations. In isolated β-cells, paxilline increased AP height by 16 mV without affecting resting membrane potential. In voltage clamp, paxilline blocked a transient component of outward current activated by a short depolarisation, which accounted for at least 90% of the initial outward K(+) current. This BK current (I(BK)) was blocked by the Ca(2+) channel blockers Cd(2+) (200 μM) or nimodipine (1 μM), and potentiated by FPL-64176 (1 μM). I(BK) was also 56% blocked by the BK channel blocker iberiotoxin (100 nM). I(BK) activated more than 10-fold faster than the delayed rectifier I(Kv) over the physiological voltage range, and partially inactivated. An AP-like command revealed that I(BK) activated and deactivated faster than I(Kv) and accounted for 86% of peak I(K), explaining why I(BK) block increased AP height. A higher amplitude AP-like command, patterned on an AP recorded in 11.1 mM glucose plus paxilline, activated 4-fold more I(Kv) and significantly increased Ca(2+) entry. Paxilline increased insulin secretion in islets exposed to 11.1 mM glucose by 67…
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The Ca2+-activated K+ component of outward current in β-cells reflects activation of large-conductance Ca2+-activated K+ (BK) channels.
“This reflects activation of large-conductance Ca2+-activated K+ channels (big K+ channels, or BK channels).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [293]
BK channel activation potentially might reduce action potential duration, Ca2+ influx and insulin release.
“This suggests BK channel activation potentially might reduce action potential duration, Ca2+ influx and insulin release.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [293]
BK channels are blocked by peptide toxins such as charybdotoxin, iberiotoxin and slotoxin, and by the alkaloid paxilline.
“They are also blocked by peptide toxins such as charybodotoxin, iberiotoxin and slotoxin (293, 311)), and by the alkaloid paxilline (293).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [293]
Blocking BK channels increases spike amplitude by approximately 20 mV and enhances GIIS.
“Indeed, blocking BK channels increases spike amplitude by ≈20 mV and enhances GIIS (293).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [293]
Some β-cells, especially those with large Ca2+ currents, possess a Ca2+-activated K+ component of outward current.
“Although the amplitude of the delayed outward current was initially thought to be largely unaffected by blocking the Ca2+ current (632), more recent data indicate that some β-cells (especially those with large Ca2+ currents) also possess a Ca2+-activated K+ component of outward current (293).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [293]
The BK channel blocker paxilline inhibits a rapidly activating and deactivating current in mouse β-cells.
“It was reported that the BK channel blocker paxilline inhibited a rapidly activating and deactivating current in mouse β-cells (293).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [293]
BK channels undergo voltage-dependent inactivation, which at -10 mV is described by a single exponential with a time constant of 20 ms.
“BK channels also undergo voltage-dependent inactivation, which at -10 mV (the peak of the action potential) is described by a single exponential with a time constant of 20 ms (293).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [293]
Rapid Ca2+-dependent inactivation of Ca2+ channels and voltage-dependent inactivation of Na+ channels during the action potential, combined with activation of Kv2.1 and BK Ca2+-activated K+ channels, underlies action potential repolarization.
“Rapid Ca2+-dependent inactivation of Ca2+ channels and voltage-dependent inactivation of Na+ channels during the action potential, combined with activation of Kv2.1 and large-conductance (BK) Ca2+-activated K+ channels, underlies action potential repolarization (293).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [293]
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Functional identification of islet cell types by electrophysiological fingerprinting
Briant, L. J. B., Zhang, Q., Vergari, E., Kellard, J. A., Rodriguez, B., Ashcroft, F. M., & Rorsman, P. (2017) · Journal of The Royal Society Interface · doi:10.1098/rsif.2016.0999 · Cited by 59 · see citing works
- Authors
- Houamed, K. M., Sweet, I. R., & Satin, L. S.
- Affiliations
- University of Michigan (US)
- University of Washington (US)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2010-09-15
- Volume
- 588
- Issue
- 18
- Pages
- 3511-3523
- ISSN
- 0022-3751 (ISSN-L)
- PMC
- PMC2988515
- OpenAlex
- W2118764705
- Cited by
- 59
- References
- 5
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 4 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 5
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- University of Washington (P30DK017047)
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (RO1DK46409, R01DK046409, P30DK017047, R01 DK 46409)
- 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
- BK channels, pancreatic beta cells, insulin secretion, potassium currents, delayed rectifier potassium current, paxilline, iberiotoxin, calcium influx, beta-cell electrical activity, islets
- MeSH terms
- Insulin Secretion, Animals, Calcium, Cell Membrane, Cells, Cultured, Evoked Potentials, Glucose, Insulin, Male, Time Factors, Insulin-Secreting Cells, Large-Conductance Calcium-Activated Potassium Channels, Mice, Electrophysiological Phenomena
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