HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 36, 25875-25881, September 8, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/36/25875    most recent M605060200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johnson, D. Articles by Bennett, E. S. Search for Related Content PubMed PubMed Citation Articles by Johnson, D. Articles by Bennett, E. S. Social Bookmarking                      What's this?

Isoform-specific Effects of the ₂ Subunit on Voltage-gated Sodium Channel Gating^*

From the Department of Molecular Pharmacology & Physiology and Programs in Cardiovascular Sciences and Neuroscience, University of South Florida College of Medicine, Tampa, Florida 33612

Voltage-gated sodium channels (Na_v) are complex glycoproteins comprised of an subunit and often one to several subunits. We have shown that sialic acid residues linked to Na_v and ₁ subunits alter channel gating. To determine whether ₂-linked sialic acids similarly impact Na_v gating, we co-expressed ₂ with Na_v1.5 or Na_v1.2 in Pro5 (complete sialylation) and in Lec2 (essentially no sialylation) cells. ₂ sialic acids caused a significant hyperpolarizing shift in Na_v1.5 voltage-dependent gating, thus describing for the first time an effect of ₂ on Na_v1.5 gating. In contrast, ₂ caused a sialic acid-independent depolarizing shift in Na_v1.2 gating. A deglycosylated mutant, _2-N, had no effect on Na_v1.5 gating, indicating further the impact of ₂ N-linked sialic acids on Na_v1.5 gating. Conversely, _2-N modulated Na_v1.2 gating virtually identically to ₂, confirming that ₂ N-linked sugars have no impact on Na_v1.2 gating. Thus, ₂ modulates Na_v gating through multiple mechanisms possibly determined by the associated subunit. ₁ and ₂ were expressed together with Na_v1.5 or Na_v1.2 in Pro5 and Lec2 cells. Together ₁ and ₂ produced a significantly larger sialic acid-dependent hyperpolarizing shift in Na_v1.5 gating. Under fully sialylating conditions, the Na_v1.2·₁·₂ complex behaved like Na_v1.2 alone. When sialylation was reduced, only the sialic acid-independent depolarizing effects of ₂ on Na_v1.2 gating were apparent. Thus, the varied effects of ₁ and ₂ on Na_v1.5 and Na_v1.2 gating are apparently synergistic and highlight the complex manner, through subunit- and sugar-dependent mechanisms, by which Na_v activity is modulated.

Received for publication, May 26, 2006 , and in revised form, July 14, 2006.

^* 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.

² To whom correspondence should be addressed: Dept. of Molecular Pharmacology and Physiology, University of South Florida, College of Medicine, MDC 8, Tampa, FL 33612. Tel.: 813-974-1545; Fax: 813-974-3079; E-mail: esbennet{at}hsc.usf.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Watanabe, D. Darbar, D. W. Kaiser, K. Jiramongkolchai, S. Chopra, B. S. Donahue, P. J. Kannankeril, and D. M. Roden Mutations in Sodium Channel {beta}1- and {beta}2-Subunits Associated With Atrial Fibrillation Circ Arrhythmia Electrophysiol, June 1, 2009; 2(3): 268 - 275. [Abstract] [Full Text] [PDF]

				D. Isaev, E. Isaeva, T. Shatskih, Q. Zhao, N. C. Smits, N. W. Shworak, R. Khazipov, and G. L. Holmes Role of Extracellular Sialic Acid in Regulation of Neuronal and Network Excitability in the Rat Hippocampus J. Neurosci., October 24, 2007; 27(43): 11587 - 11594. [Abstract] [Full Text] [PDF]