In:
The Journal of Physiology, Wiley, Vol. 592, No. 21 ( 2014-11), p. 4677-4696
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0022-3751
,
1469-7793
DOI:
10.1113/jphysiol.2014.592.issue-21
DOI:
10.1113/jphysiol.2014.274209
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2014
ZDB Id:
1475290-6
SSG:
12