Structure and function of the β2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif

Abstract

Voltage-gated sodium channels in brain neurons are complexes of a pore-forming a subunit with smaller β1 and β2 subunits. cDNA cloning and sequencing showed that the β2 subunit is a 186 residue glycoprotein with an extracellular NH 2-terminal domain containing an immunoglobulin-like fold with similarity to the neural cell adhesion molecule (CAM) contactin, a single transmembrane segment, and a small intracellular domain. Coexpression of β2 with α subunits in Xenopus oocytes increases functional expression, modulates gating, and causes up to a 4-fold increase in the capacitance of the oocyte, which results from an increase in the surface area of the plasma membrane microvilli. β2 subunits are unique among the auxiliary subunits of ion channels in combining channel modulation with a CAM motif and the ability to expand the cell membrane surface area. They may be important regulators of sodium channel expression and localization in neurons.