Sialic acids attached to N- and O-glycans within the Nav1.4 D1S5-S6 linker contribute to channel gating.
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. GENERALSIGNIFICANCE:
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.Palavras-chave
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