Journal of Biological Chemistry
Volume 281, Issue 36, 8 September 2006, Pages 25875-25881
Journal home page for Journal of Biological Chemistry

Membrane Transport, Structure, Function, and Biogenesis
Isoform-specific Effects of the β2 Subunit on Voltage-gated Sodium Channel Gating*

https://doi.org/10.1074/jbc.M605060200Get rights and content
Under a Creative Commons license
open access

Voltage-gated sodium channels (Nav) are complex glycoproteins comprised of an α subunit and often one to several β subunits. We have shown that sialic acid residues linked to Nav α and β1 subunits alter channel gating. To determine whether β2-linked sialic acids similarly impact Nav gating, we co-expressed β2 with Nav1.5 or Nav1.2 in Pro5 (complete sialylation) and in Lec2 (essentially no sialylation) cells. β2 sialic acids caused a significant hyperpolarizing shift in Nav1.5 voltage-dependent gating, thus describing for the first time an effect of β2 on Nav1.5 gating. In contrast, β2 caused a sialic acid-independent depolarizing shift in Nav1.2 gating. A deglycosylated mutant, β2-ΔN, had no effect on Nav1.5 gating, indicating further the impact of β2 N-linked sialic acids on Nav1.5 gating. Conversely, β2-ΔN modulated Nav1.2 gating virtually identically to β2, confirming that β2 N-linked sugars have no impact on Nav1.2 gating. Thus, β2 modulates Nav gating through multiple mechanisms possibly determined by the associated α subunit. β1 and β2 were expressed together with Nav1.5 or Nav1.2 in Pro5 and Lec2 cells. Together β1 and β2 produced a significantly larger sialic acid-dependent hyperpolarizing shift in Nav1.5 gating. Under fully sialylating conditions, the Nav1.2·β1·β2 complex behaved like Nav1.2 alone. When sialylation was reduced, only the sialic acid-independent depolarizing effects of β2 on Nav1.2 gating were apparent. Thus, the varied effects of β1 and β2 on Nav1.5 and Nav1.2 gating are apparently synergistic and highlight the complex manner, through subunit- and sugar-dependent mechanisms, by which Nav activity is modulated.

Cited by (0)

*

This work was supported in part by NIAMS, National Institutes of Health Grant R-01AR45169 (to E. S. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1

Present address: Faculty of Life Sciences, University of Manchester, 2nd Floor, Core Technology Facility, 46 Grafton St., Manchester, M13 9NT, UK.