Document Type
Article
Publication Date
5-2020
Abstract
N-type inactivation of voltage-gated K+ channels is conferred by the N-terminal “ball” domains of select pore-forming α subunits or of auxiliary β subunits, and influences electrical cellular excitability. Here, we show that hemin impairs inactivation of K+ channels formed by Kv3.4 α subunits as well as that induced by the subunits Kvβ1.1, Kvβ1.2, and Kvβ3.1 when coexpressed with α subunits of the Kv1 subfamily. In Kvβ1.1, hemin interacts with cysteine and histidine residues in the N terminus (C7 and H10) with high affinity (EC50 100 nM). Similarly, rapid inactivation of Kv4.2 channels induced by the dipeptidyl peptidase-like protein DPP6a is also sensitive to hemin, and the DPP6a mutation C13S eliminates this dependence. The results suggest a common mechanismfor a dynamic regulation of Kv channel inactivation by heme/hemin in N-terminal ball domains of Kv α and auxiliary β subunits. Free intracellular heme therefore has the potential to regulate cellular excitability via modulation of Kv channel inactivation.
Recommended Citation
Coburger, I., Yang, K., Bernert, A. et al. Impact of intracellular hemin on N-type inactivation of voltage-gated K+ channels. Pflugers Arch - Eur J Physiol 472, 551–560 (2020). https://doi.org/10.1007/s00424-020-02386-1
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
First Page
551
Last Page
560
Publication Title
Pflügers Archiv - European Journal of Physiology
DOI
10.1007/s00424-020-02386-1
Comments
© The Author(s) 2020. Original published version available at https://doi.org/10.1007/s00424-020-02386-1