Characterization of voltage‐dependent sodium and calcium channels in mouse pancreatic A‐ and B‐cells
Open accessAbstract
Insulin and glucagon are the major hormones of the islets of Langerhans that are stored and released from the B- and A-cells, respectively. Both hormones are secreted when the intracellular cytosolic Ca2+ concentration ([Ca2+]i) increases. The [Ca2+]i is modulated by mutual inhibition and activation of different voltage-gated ion channels. The precise interplay of these ion channels in either glucagon or insulin release is unknown, owing in part to the difficulties in distinguishing A- from B-cells in electrophysiological experiments. We have established a single-cell RT-PCR method to identify A- and B-cells from the mouse. A combination of PCR, RT-PCR, electrophysiology and pharmacology enabled us to characterize the different sodium and calcium channels in mouse islet cells. In both A- and B-cells, 60% of the inward calcium current (I(Ca)) is carried by L-type calcium channels. In B-cells, the predominant calcium channel is Ca(v)1.2, whereas Ca(v)1.2 and Ca(v)1.3 were identified in A-cells. These results were confirmed by using mice carrying A- or B-cell-specific inactivation of the Ca(v)1.2 gene. In B-cells, the remaining I(Ca) flows in equal amounts through Ca(v)2.1, Ca(v)2.2 and Ca(v)2.3. In A-cells, 30 and 15% of I(Ca) is due to Ca(v)2.3 and Ca(v)2.1 activity, respectively, whereas Ca(v)2.2 current was not found in these cells. Low-voltage-activated T-type calcium channels could not be identified in A- and B-cells. Instead, two TTX-sensitive sodium currents were found:…
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In ~30% of β-cells an additional Na+ current component is present, accounting for 15-25% of the total Na+ current (~150 pA), with inactivation half-complete at -40 mV, persisting at physiological membrane potentials and capable of contributing to the upstroke of the action potential.
“Not all β-cells conform to this picture, however: in ~30% of β-cells an additional Na+ current component is present, which accounts for 15-25% of the total Na+ current (i.e. ~150 pA) (709, 761). As its inactivation is half-complete at -40 mV, this Na+ current component persists at physiological membrane potentials and is therefore capable of contributing to the upstroke of the action potential (76”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [709]
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InfluentialCaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum
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BackgroundRegulation of Insulin Granule Exocytosis
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Voltage-gated calcium channels in GtoPdb v.2021.2
Catterall, W., Perez-Reyes, E., Snutch, T., & Striessnig, J. (2021) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f80/2021.2 · Cited by 2 · see citing works
Ion Channels and Insulin Secretion
Jacobson, D., & Philipson, L. (2008) · Springer eBooks · doi:10.1007/978-4-431-75452-7_6 · Cited by 2 · see citing works
Mathematical models and multiscale simulations of cellular secretion processes
González‐Vélez, V. (2011) · doi:10.5821/dissertation-2117-94768
“Sodium channels activate and inactivate as a function of membrane potential with a threshold voltage in the range of -30 to -20 mV [76, 9, 186].”
BackgroundVoltage-gated calcium channels (CaV) in GtoPdb v.2025.3
Catterall, W., Pérez-Reyes, E., Snutch, T. P., & Striessnig, J. (2025) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f80/2025.3
The right stuff: beta-cell channels, cycles, and sensors.
Halban, P. (2008) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.90692.2008
Prevention of type 1 diabetes by carbamazepine in non-obese diabetic mice
Lee, J. T. C. (2017) · doi:10.14288/1.0354479
“Although VGSCs in mice seem to play a relatively minor role, knockout of Scn1b subunit impairs GSIS and results in glucose intolerance (188).”
BackgroundInfluentialIdentification and characterization of pancreatic beta-cell survival factors
Yang, Y. (2014) · doi:10.14288/1.0103408
“7 in mouse islet cells (140), and further indicated that Nav1.”
BackgroundNelson, P. L. (2010) · doi:10.31390/gradschool_theses.3041
“The identification of the non-L-type VDCCs is still unclear but may be T-, N-, R-, or P-types depending on the species and the particular study (Gopel et al., 2000; Gromada et al., 1997; Vignali et al., 2006).”
Background
- Authors
- Vignali, S., Leiss, V., Karl, R., Hofmann, F., & Welling, A.
- Affiliations
- Technical University of Munich (DE)
- ORCID
- Hofmann, Franz
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2006-04-21
- Volume
- 572
- Issue
- 3
- Pages
- 691-706
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC1780015
- OpenAlex
- W1574747114
- Cited by
- 96
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 6 · 2014: 13 · 2013: 4 · 2012: 10
- FWCI
- 6.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- Fonds der Chemischen Industrie
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- voltage-gated sodium channels, voltage-gated calcium channels, pancreatic A cells, pancreatic beta cells, pancreatic islets, insulin secretion, glucagon secretion, L-type calcium channels, Cav1.2, Cav1.3, Cav2.1, CaV2.2, Cav2.3, T-type calcium channels, Nav1.7, single-cell RT-PCR
- MeSH terms
- Animals, Cells, Cultured, Membrane Potentials, Tissue Distribution, Calcium Channels, Sodium Channels, Ion Channel Gating, Glucagon-Secreting Cells, Insulin-Secreting Cells, Mice
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