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 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 mechan

SUBMITTER: Coburger I 

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

REPOSITORIES: biostudies-literature