Details

Autor(en) / Beteiligte

• Schwetz, Tara A.
• Norring, Sarah A.
• Ednie, Andrew R.
• Bennett, Eric S.

Titel

Sialic Acids Attached to O-Glycans Modulate Voltage-gated Potassium Channel Gating

Ist Teil von

• The Journal of biological chemistry, 2011-02, Vol.286 (6), p.4123-4132

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (Kv) 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 Kv2.1, Kv4.2, and Kv4.3. 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 Kv 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 Kv4.2 and Kv4.3 cannot be N-glycosylated, and immunoblot analysis confirmed Kv2.1 is not N-glycosylated. Glycosidase gel shift analysis suggested that Kv2.1, Kv4.2, and Kv4.3 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 Kv channel isoforms using Cu(I)-catalyzed cycloaddition chemistry. Together, the data indicate that sialic acids attached to O-glycans uniquely modulate gating of three Kv 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 Kv channel function and thereby contribute to changes in electrical signaling that result from regulated ion channel expression and/or O-glycosylation.