Zhang, Q., Chibalina, M.V., Bengtsson, M. et al. (12 more authors) (2014) Na+ current properties in islet α- and β-cells reflect cell-specific Scn3a and Scn9a expression. The Journal of Physiology, 592 (21). pp. 4677-4696. ISSN 0022-3751
Abstract
Key points
α‐ and β‐cells express both Nav1.3 and Nav1.7 Na+ channels but in different relative amounts.
The differential expression explains the different properties of Na+ currents in α‐ and β‐cells.
Nav1.3 is the functionally important Na+ channel α subunit in both α‐ and β‐cells.
Islet Nav1.7 channels are locked in an inactive state due to an islet cell‐specific factor.
Mouse pancreatic β‐ and α‐cells are equipped with voltage‐gated Na+ currents that inactivate over widely different membrane potentials (half‐maximal inactivation (V0.5) at −100 mV and −50 mV in β‐ and α‐cells, respectively). Single‐cell PCR analyses show that both α‐ and β‐cells have Nav1.3 (Scn3) and Nav1.7 (Scn9a) α subunits, but their relative proportions differ: β‐cells principally express Nav1.7 and α‐cells Nav1.3. In α‐cells, genetically ablating Scn3a reduces the Na+ current by 80%. In β‐cells, knockout of Scn9a lowers the Na+ current by >85%, unveiling a small Scn3a‐dependent component. Glucagon and insulin secretion are inhibited in Scn3a−/− islets but unaffected in Scn9a‐deficient islets. Thus, Nav1.3 is the functionally important Na+ channel α subunit in both α‐ and β‐cells because Nav1.7 is largely inactive at physiological membrane potentials due to its unusually negative voltage dependence of inactivation. Interestingly, the Nav1.7 sequence in brain and islets is identical and yet the V0.5 for inactivation is >30 mV more negative in β‐cells. This may indicate the presence of an intracellular factor that modulates the voltage dependence of inactivation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited (http://creativecommons.org/licenses/by/4.0/). |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 10 Sep 2020 06:17 |
Last Modified: | 10 Sep 2020 06:17 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1113/jphysiol.2014.274209 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:165326 |