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Na + current properties in islet α‐ and β‐cells reflect cell‐specific Scn3a and Scn9a expression
Author(s) -
Zhang Quan,
Chibalina Margarita V.,
Bengtsson Martin,
Groschner Lukas N.,
Ramracheya Reshma,
Rorsman Nils J. G.,
Leiss Veronika,
Nassar Mohammed A.,
Welling Andrea,
Gribble Fiona M.,
Reimann Frank,
Hofmann Franz,
Wood John N.,
Ashcroft Frances M.,
Rorsman Patrik
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.274209
Subject(s) - islet , intracellular , membrane potential , protein subunit , microbiology and biotechnology , biophysics , chemistry , biology , patch clamp , membrane , electrophysiology , endocrinology , insulin , biochemistry , gene , neuroscience
Key points α‐ and β‐cells express both Na v 1.3 and Na v 1.7 Na + channels but in different relative amounts. The differential expression explains the different properties of Na + currents in α‐ and β‐cells. Na v 1.3 is the functionally important Na + channel α subunit in both α‐ and β‐cells. Islet Na v 1.7 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 ( V 0.5 ) at −100 mV and −50 mV in β‐ and α‐cells, respectively). Single‐cell PCR analyses show that both α‐ and β‐cells have Na v 1.3 ( Scn3 ) and Na v 1.7 ( Scn9a ) α subunits, but their relative proportions differ: β‐cells principally express Na v 1.7 and α‐cells Na v 1.3. 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, Na v 1.3 is the functionally important Na + channel α subunit in both α‐ and β‐cells because Na v 1.7 is largely inactive at physiological membrane potentials due to its unusually negative voltage dependence of inactivation. Interestingly, the Na v 1.7 sequence in brain and islets is identical and yet the V 0.5 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.