title: Independent and joint modulation of rat Nav1.6 voltage-gated sodium channels by coexpression with the auxiliary β1 and β2 subunits.
abstract: The Na(v)1.6 voltage-gated sodium channel α subunit isoform is the most abundant isoform in the brain and is implicated in the transmission of high frequency action potentials. Purification and immunocytochemical studies imply that Na(v)1.6 exist predominantly as Na(v)1.6+β1+β2 heterotrimeric complexes. We assessed the independent and joint effects of the rat β1 and β2 subunits on the gating and kinetic properties of rat Na(v)1.6 channels by recording whole-cell currents in the two-electrode voltage clamp configuration following transient expression in Xenopus oocytes. The β1 subunit accelerated fast inactivation of sodium currents but had no effect on the voltage dependence of their activation and steady-state inactivation and also prevented the decline of currents following trains of high-frequency depolarizing prepulses. The β2 subunit selectively retarded the fast phase of fast inactivation and shifted the voltage dependence of activation towards depolarization without affecting other gating properties and had no effect on the decline of currents following repeated depolarization. The β1 and β2 subunits expressed together accelerated both kinetic phases of fast inactivation, shifted the voltage dependence of activation towards hyperpolarization, and gave currents with a persistent component typical of those recorded from neurons expressing Na(v)1.6 sodium channels. These results identify unique effects of the β1 and β2 subunits and demonstrate that joint modulation by both auxiliary subunits gives channel properties that are not predicted by the effects of individual subunits.
authors: Cornell University, Department of Entomology, New York State Agricultural Experiment Station, Geneva, NY 14456, USA.
authors: Jianguo
authors: J
authors: Tan
authors: David M
authors: DM
authors: Soderlund
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009865:Oocytes; D055550:Protein Stability; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; D021122:Protein Subunits; C507811:Scn8a protein, rat; D015222:Sodium Channels