Document Detail

Isoform-specific effects of the beta2 subunit on voltage-gated sodium channel gating.
MedLine Citation:
PMID:  16847056     Owner:  NLM     Status:  MEDLINE    
Voltage-gated sodium channels (Nav) are complex glycoproteins comprised of an alpha subunit and often one to several beta subunits. We have shown that sialic acid residues linked to Nav alpha and beta1 subunits alter channel gating. To determine whether beta2-linked sialic acids similarly impact Nav gating, we co-expressed beta2 with Nav1.5 or Nav1.2 in Pro5 (complete sialylation) and in Lec2 (essentially no sialylation) cells. Beta2 sialic acids caused a significant hyperpolarizing shift in Nav1.5 voltage-dependent gating, thus describing for the first time an effect of beta2 on Nav1.5 gating. In contrast, beta2 caused a sialic acid-independent depolarizing shift in Nav1.2 gating. A deglycosylated mutant, beta(2-DeltaN), had no effect on Nav1.5 gating, indicating further the impact of beta2 N-linked sialic acids on Nav1.5 gating. Conversely, beta(2-DeltaN) modulated Nav1.2 gating virtually identically to beta2, confirming that beta2 N-linked sugars have no impact on Nav1.2 gating. Thus, beta2 modulates Nav gating through multiple mechanisms possibly determined by the associated alpha subunit. Beta1 and beta2 were expressed together with Nav1.5 or Nav1.2 in Pro5 and Lec2 cells. Together beta1 and beta2 produced a significantly larger sialic acid-dependent hyperpolarizing shift in Nav1.5 gating. Under fully sialylating conditions, the Nav1.2.beta1.beta2 complex behaved like Nav1.2 alone. When sialylation was reduced, only the sialic acid-independent depolarizing effects of beta2 on Nav1.2 gating were apparent. Thus, the varied effects of beta1 and beta2 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.
Daniel Johnson; Eric S Bennett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-07-17
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-04     Completed Date:  2006-12-18     Revised Date:  2011-07-22    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25875-81     Citation Subset:  IM    
Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida 33612, USA.
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MeSH Terms
CHO Cells
Ion Channel Gating / physiology*
Membrane Potentials / physiology
Muscle Proteins / genetics,  metabolism*
Nerve Tissue Proteins / genetics,  metabolism*
Patch-Clamp Techniques
Protein Isoforms / genetics,  metabolism*
Protein Subunits / genetics,  metabolism*
Recombinant Fusion Proteins / genetics,  metabolism
Sialic Acids / metabolism*
Sodium Channels / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Muscle Proteins; 0/Nerve Tissue Proteins; 0/Protein Isoforms; 0/Protein Subunits; 0/Recombinant Fusion Proteins; 0/SCN2B protein, human; 0/Sialic Acids; 0/Sodium Channels; 0/sodium channel protein type 5 subunit alpha; 0/sodium channel, voltage-gated, type II, alpha 1 subunit

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