ArticleThe Journal of physiology2010
Calcium-activated and voltage-gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses.
Article in The Journal of physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 71 citations in OpenAlex.
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- KCNB1-Leptin receptor complexes couple electric and endocrine function in the melanocortin neurons of the hypothalamus.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells.JCI insight · 2024Article
- RyR2 regulates store-operated Ca2+ entry, phospholipase C activity, and electrical excitability in the insulinoma cell line INS-1.PloS one · 2023Article
- BK Channel in the Physiology and in the Cancer of Pancreatic Duct: Impact and Reliability of BK Openers.Frontiers in pharmacology · 2022Review
- Beta-Cell Ion Channels and Their Role in Regulating Insulin Secretion.Comprehensive Physiology · 2021Review
- The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on [Formula: see text] dynamics.Scientific reports · 2021Article
- Regulatory effects of protein S-acylation on insulin secretion and insulin action.Open biology · 2021Review
- Temporal Transcriptome Analysis Reveals Dynamic Gene Expression Patterns Driving β-Cell Maturation.Frontiers in cell and developmental biology · 2021Article
- SP6616 as a Kv2.1 inhibitor efficiently ameliorates peripheral neuropathy in diabetic mice.EBioMedicine · 2020Article
- Aging, hormones and receptors.Physiological research · 2020Review
- Article
- Ion Channels of the Islets in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Possible New Strategies for the Treatment of Congenital Hyperinsulinism.Frontiers in endocrinology · 2020Article
- Insulin Release Mechanism Modulated by Toxins Isolated from Animal Venoms: From Basic Research to Drug Development Prospects.Molecules (Basel, Switzerland) · 2019Review
- Glucose-mediated inhibition of calcium-activated potassium channels limits α-cell calcium influx and glucagon secretion.American journal of physiology. Endocrinology and metabolism · 2019Article
- Optical tools for understanding the complexity of β-cell signalling and insulin release.Nature reviews. Endocrinology · 2018Review
- High-fat-diet-induced remission of diabetes in a subset of KDiabetes, obesity & metabolism · 2018Article
- Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the CaDevelopmental cell · 2018Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Glucose-induced β-cell action potential (AP) repolarization is regulated by potassium efflux through voltage gated (Kv) and calcium activated (K(Ca)) potassium channels. Thus, ablation of the primary Kv channel of the β-cell, Kv2.1, causes increased AP duration. However, Kv2.1(-/-) islet electrical activity still remains sensitive to the potassium channel inhibitor tetraethylammonium. Therefore, we utilized Kv2.1(-/-) islets to characterize Kv and K(Ca) channels and their respective roles in modulating the β-cell AP. The remaining Kv current present in Kv2.1(-/-) β-cells is inhibited with 5 μM CP 339818. Inhibition of the remaining Kv current in Kv2.1(-/-) mouse β-cells increased AP firing frequency by 39.6% but did not significantly enhance glucose stimulated insulin secretion (GSIS). The modest regulation of islet AP frequency by CP 339818 implicates other K(+) channels, possibly K(Ca) channels, in regulating AP repolarization. Blockade of the K(Ca) channel BK with slotoxin increased β-cell AP amplitude by 28.2%, whereas activation of BK channels with isopimaric acid decreased β-cell AP amplitude by 30.6%. Interestingly, the K(Ca) channel SK significantly contributes to Kv2.1(-/-) mouse islet AP repolarization. Inhibition of SK channels decreased AP firing frequency by 66% and increased AP duration by 67% only when Kv2.1 is ablated or inhibited and enhanced GSIS by 2.7-fold. Human islets also express SK3 channels and their β-cell AP frequency is significantly accelerated by 4.8-fold with apamin. These results uncover important repolarizing roles for both Kv and K(Ca) channels and identify distinct roles for SK channel activity in regulating calcium- versus sodium-dependent AP firing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.