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

Journal Article (Journal Article)

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 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.

Full Text

Duke Authors

Cited Authors

  • Coburger, I; Yang, K; Bernert, A; Wiesel, E; Sahoo, N; Swain, SM; Hoshi, T; Schönherr, R; Heinemann, SH

Published Date

  • May 2020

Published In

Volume / Issue

  • 472 / 5

Start / End Page

  • 551 - 560

PubMed ID

  • 32388729

Pubmed Central ID

  • PMC7239824

Electronic International Standard Serial Number (EISSN)

  • 1432-2013

Digital Object Identifier (DOI)

  • 10.1007/s00424-020-02386-1

Language

  • eng

Conference Location

  • Germany