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Sialic acids attached to N- and O-glycans within the Nav1.4 D1S5-S6 linker contribute to channel gating.
Ednie, Andrew R; Harper, Jean M; Bennett, Eric S.
Afiliação
  • Ednie AR; Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
  • Harper JM; Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
  • Bennett ES; Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA. Electronic address: esbennet@health.usf.edu.
Biochim Biophys Acta ; 1850(2): 307-17, 2015 Feb.
Article em En | MEDLINE | ID: mdl-25450184
ABSTRACT

BACKGROUND:

Voltage-gated Na+ channels (Nav) are responsible for the initiation and conduction of neuronal and muscle action potentials. Nav gating can be altered by sialic acids attached to channel N-glycans, typically through isoform-specific electrostatic mechanisms.

METHODS:

Using two sets of Chinese Hamster Ovary cell lines with varying abilities to glycosylate glycoproteins, we show for the first time that sialic acids attached to O-glycans and N-glycans within the Nav1.4 D1S5-S6 linker modulate Nav gating.

RESULTS:

All measured steady-state and kinetic parameters were shifted to more depolarized potentials under conditions of essentially no sialylation. When sialylation of only N-glycans or of only O-glycans was prevented, the observed voltage-dependent parameter values were intermediate between those observed under full versus no sialylation. Immunoblot gel shift analyses support the biophysical data.

CONCLUSIONS:

The data indicate that sialic acids attached to both N- and O-glycans residing within the Nav1.4 D1S5-S6 linker modulate channel gating through electrostatic mechanisms, with the relative contribution of sialic acids attached to N- versus O-glycans on channel gating being similar. GENERAL

SIGNIFICANCE:

Protein N- and O-glycosylation can modulate ion channel gating simultaneously. These data also suggest that environmental, metabolic, and/or congenital changes in glycosylation that impact sugar substrate levels, could lead, potentially, to changes in Nav sialylation and gating that would modulate AP waveforms and conduction.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Siálicos / Glicoproteínas / Ativação do Canal Iônico / Canal de Sódio Disparado por Voltagem NAV1.4 Limite: Animals Idioma: En Revista: Biochim Biophys Acta Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Siálicos / Glicoproteínas / Ativação do Canal Iônico / Canal de Sódio Disparado por Voltagem NAV1.4 Limite: Animals Idioma: En Revista: Biochim Biophys Acta Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos