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J Physiol. 2014 Nov 1;592(21):4677-96. doi: 10.1113/jphysiol.2014.274209. Epub 2014 Aug 28.

Na+ current properties in islet α- and β-cells reflect cell-specific Scn3a and Scn9a expression.

Author information

1
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.
2
Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, 80802, München, Germany Institut für Pharmakologie und Toxikologie, Eberhard-Karls Universität, Wilhelmstr. 56, 72074, Tübingen, Germany.
3
Molecular Nociception Group, University College London (UCL), Gower Street, London, WC1E 6BT, UK Biomedical Science, University of Sheffield, Sheffield, S10 2TN, UK.
4
Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, 80802, München, Germany.
5
Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK.
6
Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, 80802, München, Germany FOR 923, Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, 80802, München, Germany.
7
Molecular Nociception Group, University College London (UCL), Gower Street, London, WC1E 6BT, UK.
8
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
9
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK Department of Neuroscience and Physiology, Sahlgren's Academy, University of Göteborg, Box 430, SE40530, Göteborg, Sweden patrik.rorsman@ocdem.ox.ac.uk.

Abstract

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.

PMID:
25172946
PMCID:
PMC4253470
DOI:
10.1113/jphysiol.2014.274209
[Indexed for MEDLINE]
Free PMC Article

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