Cited by 209Pancreatic function and diabetesCellular transport and secretionIon channel regulation and function

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Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells.

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Barg, S, Galvanovskis, J, Göpel, S O, Rorsman, P, Eliasson, L·2000·Diabetes

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Abstract

alpha-Cells were identified in preparations of dispersed mouse islets by immunofluorescence microscopy. A high fraction of alpha-cells correlated with a small cell size measured as the average cell diameter (10 microm) and whole-cell capacitance (<4 pF). The alpha-cells generated action potentials at a low frequency (1 Hz) in the absence of glucose. These action potentials were reversibly inhibited by elevation of the glucose concentration to 20 mmol/l. The action potentials originated from a membrane potential more negative than -50 mV, had a maximal upstroke velocity of 5 V/s, and peaked at +1 mV. Voltage-clamp experiments revealed the ionic conductances underlying the generation of action potentials. alpha-Cells are equipped with a delayed tetraethyl-ammonium-blockable outward current (activating at voltages above -20 mV), a large tetrodotoxin-sensitive Na+ current (above -30 mV; peak current 200 pA at +10 mV), and a small Ca2+ current (above -50 mV; peak current 30 pA at +10 mV). The latter flowed through omega-conotoxin GVIA (25%)- and nifedipine-sensitive (50%) Ca(2+)-channels. Mouse alpha-cells contained, on average, 7,300 granules, which undergo Ca(2+)-induced exocytosis when the alpha-cell is depolarized. Three functional subsets of granules were identified, and the size of the immediately releasable pool was estimated as 80 granules, or 1% of the total granule number. The maximal rate of exocytosis (1.5 pF/s) was observed 21 ms after the onset of the voltage-clamp depolarization, which is precisely the duration of Ca(2+)-influx during an action potential. Our results suggest that the secretory machinery of the alpha-cell is optimized for maximal efficiency in the use of Ca2+ for exocytosis.

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Authors: Barg, S., Galvanovskis, J., Göpel, S. O., Rorsman, P., & Eliasson, L.
Affiliations: Lund University (SE)
ORCID: Barg, S
Rorsman, P
Eliasson, L
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2000-09-01
Volume: 49
Issue: 9
Pages: 1500-1510
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.49.9.1500
OpenAlex: W2163595098
Cited by: 209
References: 30
Citations by year: 2026: 6 · 2025: 6 · 2024: 2 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 12 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 9 · 2015: 3 · 2014: 10 · 2013: 10 · 2012: 12
FWCI: 3.55
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Lund University Publications (Lund University) (submittedVersion)
Funders: Fondation pour la Recherche Médicale
Knut och Alice Wallenbergs Stiftelse
Novo Nordisk
Direktör Albert Påhlssons Stiftelse
Magnus Bergvalls Stiftelse
Medical Research Council
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords: alpha cells, glucagon secretion, exocytosis, action potential, calcium channels, calcium-induced exocytosis, secretory granules, pancreatic islets, sodium current, tetrodotoxin-sensitive sodium current, omega-conotoxin GVIA, secretory machinery
MeSH terms: Animals, Cells, Cultured, Cytoplasmic Granules, Diazoxide, Exocytosis, Glucagon, Islets of Langerhans, Membrane Potentials, Mice, Inbred Strains, Tetrodotoxin, Tolbutamide, Sodium Channels, Mice

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Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells.

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