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

ABSTRACT: N-type inactivation of voltage-gated K+ channels is conferred by the N-terminal "ball" domains of select pore-forming ? subunits or of auxiliary ? subunits, and influences electrical cellular excitability. Here, we show that hemin impairs inactivation of K+ channels formed by Kv3.4 ? subunits as well as that induced by the subunits Kv?1.1, Kv?1.2, and Kv?3.1 when coexpressed with ? subunits of the Kv1 subfamily. In Kv?1.1, 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 ? and auxiliary ? subunits. Free intracellular heme therefore has the potential to regulate cellular excitability via modulation of Kv channel inactivation.

SUBMITTER: Coburger I 

PROVIDER: S-EPMC7239824 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature