title: Physiologic and pathophysiologic consequences of altered sialylation and glycosylation on ion channel function.
abstract: Voltage-gated ion channels are transmembrane proteins that regulate electrical excitability in cells and are essential components of the electrically active tissues of nerves, muscle and the heart. Potassium channels are one of the largest subfamilies of voltage sensitive channels and are among the most-studied of the voltage-gated ion channels. Voltage-gated channels can be glycosylated and changes in the glycosylation pattern can affect ion channel function, leading to neurological and neuromuscular disorders and congenital disorders of glycosylation (CDG). Alterations in glycosylation can also be acquired and appear to play a role in development and aging. Recent studies have focused on the impact of glycosylation and sialylation on ion channels, particularly for voltage-gated potassium and sodium channels. The terminal step of sialylation often affects channel activation and inactivation kinetics. The presence of sialic acids on O or N-glycans can alter the gating mechanism and cause conformational changes in the voltage-sensing domains due to sialic acid's negative charges. This manuscript will provide an overview of sialic acids, potassium and sodium channel function, and the impact of sialylation on channel activation and deactivation.
authors: Chemical and Biomolecular Engineering, Johns Hopkins University, United States. Electronic address: denizbaycin@gmail.com.
authors: Deniz
authors: D
authors: Baycin-Hizal
authors: Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, United States.
authors: Allan
authors: A
authors: Gottschalk
authors: Chemical and Biomolecular Engineering, Johns Hopkins University, United States.
authors: Elena
authors: E
authors: Jacobson
authors: Chemical and Biomolecular Engineering, Johns Hopkins University, United States.
authors: Sunny
authors: S
authors: Mai
authors: Chemical and Biomolecular Engineering, Johns Hopkins University, United States.
authors: Daniel
authors: D
authors: Wolozny
authors: Pathology, Johns Hopkins University, United States.
authors: Hui
authors: H
authors: Zhang
authors: Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, United States.
authors: Sharon S
authors: SS
authors: Krag
authors: Chemical and Biomolecular Engineering, Johns Hopkins University, United States.
authors: Michael J
authors: MJ
authors: Betenbaugh
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D018981:Congenital Disorders of Glycosylation / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D048788:Growth and Development / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D007473:Ion Channels; D015221:Potassium Channels; D019158:N-Acetylneuraminic Acid
keywords: Congenital disorders of glycosylation; Glycosylation; Neurological disorders; Sialylation; Voltage-gated potassium channels; Voltage-gated sodium channels