| First Author | Zhang Q | Year | 2014 |
| Journal | J Physiol | Volume | 592 |
| Issue | 21 | Pages | 4677-96 |
| PubMed ID | 25172946 | Mgi Jnum | J:226211 |
| Mgi Id | MGI:5696491 | Doi | 10.1113/jphysiol.2014.274209 |
| Citation | Zhang Q, et al. (2014) Na+ current properties in islet alpha- and beta-cells reflect cell-specific Scn3a and Scn9a expression. J Physiol 592(Pt 21):4677-96 |
| abstractText | Mouse pancreatic beta- and alpha-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 beta- and alpha-cells, respectively). Single-cell PCR analyses show that both alpha- and beta-cells have Nav1.3 (Scn3) and Nav1.7 (Scn9a) alpha subunits, but their relative proportions differ: beta-cells principally express Nav1.7 and alpha-cells Nav1.3. In alpha-cells, genetically ablating Scn3a reduces the Na(+) current by 80%. In beta-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 alpha subunit in both alpha- and beta-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 beta-cells. This may indicate the presence of an intracellular factor that modulates the voltage dependence of inactivation. |
