The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells.
Open accessAbstract
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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“The small store-operated current is sufficient to trigger voltagedependent Ca 2+ influx because of the high input resistance [12] and the fact that the action potentials start at voltages as negative as -60 mV [13,39,43].”
From Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells (2007) · cites this paper as [12]
In the citing paper
“mouse ␣-cells show little K ATP channel expression (25,26), corresponding to 2% of that in mouse -cells (27).”
From Paradoxical Stimulation of Glucagon Secretion by High Glucose Concentrations (2006) · cites this paper as [27]
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“the sugar hyperpolarizes mouse ␣-cells (14,27,29) and, as now confirmed, lowers [Ca 2ϩ ] i (14).”
From Paradoxical Stimulation of Glucagon Secretion by High Glucose Concentrations (2006) · cites this paper as [27]
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Metadata
- Authors
- Barg, S., Galvanovskis, J., Göpel, S. O., Rorsman, P., & Eliasson, L.
- Affiliations
- Lund University (SE)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-09-01
- Volume
- 49
- Issue
- 9
- Pages
- 1500-1510
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- 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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