Publication

N-glycosylation modulates the inactivation kinetics of the Kv3.4 ion channel

2025

Abstract

In our previous study, when mapping the kinetics of all 40 genetic subtypes of the voltage-gated potassium (Kv) family of ion channels, we observed significant heterogeneity in the inactivation delay of Kv3.4. Kv3.4 enables high-frequency firing in excitable cells and is linked to disorders such as Alzheimer's disease, epilepsy, chronic pain, and cardiovascular disease. In this study, we found that N-glycosylation, a co- and post-translational process of adding glycans branches to proteins, is a key mechanism that causes heterogeneity in the inactivation delay of Kv3.4 ion channel. Additionally, we discovered that changes in glucose availability directly affect N-glycosylation and the kinetics of Kv3.4, along with other N-glycosylated Kvs, making glucose a key regulator of Kv activity and, consequently, cell excitability. We propose that disruptions in N-glycosylation of Kv3.4 ion channels may play a role in neurological disorders linked to impaired glucose metabolism.

Official source

https://infoscience.epfl.ch/entities/publication/9090b84e-67b4-4a5d-bd69-c4098e7ad246

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2025

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/9090b84e-67b4-4a5d-bd69-c4098e7ad246

About this result

Related concepts (32)

Voltage-gated ion channel

Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change.

Ion channel

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

Potassium channel

Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions. Potassium channels function to conduct potassium ions down their electrochemical gradient, doing so both rapidly (up to the diffusion rate of K+ ions in bulk water) and selectively (excluding, most notably, sodium despite the sub-angstrom difference in ionic radius).

Related publications (10)

N-glycosylation modulates the inactivation kinetics of the Kv3.4 ion channel

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