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J Biol Chem. 2011 Feb 11;286(6):4123-32. doi: 10.1074/jbc.M110.171322. Epub 2010 Nov 29.

Sialic acids attached to O-glycans modulate voltage-gated potassium channel gating.

Author information

  • 1Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida 33612, USA.

Abstract

Neuronal, cardiac, and skeletal muscle action potentials are produced and conducted through the highly regulated activity of several types of voltage-gated ion channels. Voltage-gated potassium (K(v)) channels are responsible for action potential repolarization. Glycans can be attached to glycoproteins through N- and O-linkages. Previous reports described the impact of N-glycans on voltage-gated ion channel function. Here, we show that sialic acids attached through O-linkages modulate gating of K(v)2.1, K(v)4.2, and K(v)4.3. The conductance-voltage (G-V) relationships for each isoform were shifted uniquely by a depolarizing 8-16 mV under conditions of reduced sialylation. The data indicate that sialic acids modulate K(v) channel activation through apparent electrostatic mechanisms that promote channel activity. Voltage-dependent steady-state inactivation was unaffected by changes in sialylation. N-Linked sialic acids cannot be responsible for the G-V shifts because K(v)4.2 and K(v)4.3 cannot be N-glycosylated, and immunoblot analysis confirmed K(v)2.1 is not N-glycosylated. Glycosidase gel shift analysis suggested that K(v)2.1, K(v)4.2, and K(v)4.3 were O-glycosylated and sialylated. To confirm this, azide-modified sugar residues involved specifically in O-glycan and sialic acid biosynthesis were shown to incorporate into all three K(v) channel isoforms using Cu(I)-catalyzed cycloaddition chemistry. Together, the data indicate that sialic acids attached to O-glycans uniquely modulate gating of three K(v) channel isoforms that are not N-glycosylated. These data provide the first evidence that external O-glycans, with core structures distinct from N-glycans in type and number of sugar residues, can modulate K(v) channel function and thereby contribute to changes in electrical signaling that result from regulated ion channel expression and/or O-glycosylation.

PMID:
21115483
[PubMed - indexed for MEDLINE]
PMCID:
PMC3039321
Free PMC Article

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