Impact of intracellular hemin on N-type inactivation of voltage-gated K + channels.

Autor: Coburger I; Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Str. 2, D-07745, Jena, Germany., Yang K; Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Str. 2, D-07745, Jena, Germany., Bernert A; Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Str. 2, D-07745, Jena, Germany., Wiesel E; Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Str. 2, D-07745, Jena, Germany., Sahoo N; Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Str. 2, D-07745, Jena, Germany.; Department of Biology, The University of Texas Rio Grande Valley, 1201 West University Drive, Edinburg, TX, 78539, USA., Swain SM; Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Str. 2, D-07745, Jena, Germany.; Department of Medicine, Duke University and Durham VA Medical Centers, Durham, NC, 27710, USA., Hoshi T; Department of Physiology, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA, 19104-6085, USA., Schönherr R; Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Str. 2, D-07745, Jena, Germany., Heinemann SH; Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Str. 2, D-07745, Jena, Germany. Stefan.H.Heinemann@uni-jena.de.
Jazyk: angličtina
Zdroj: Pflugers Archiv : European journal of physiology [Pflugers Arch] 2020 May; Vol. 472 (5), pp. 551-560. Date of Electronic Publication: 2020 May 10.
DOI: 10.1007/s00424-020-02386-1
Abstrakt: 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 (EC 50 100 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 mechanism for 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.
Databáze: MEDLINE
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