@Article{dbt_mods_00057185,
  author = 	{Coburger, Ina
		and Yang, Kefan
		and Bernert, Alisa
		and Wiesel, Eric
		and Sahoo, Nirakar
		and Swain, Sandip M.
		and Hoshi, Toshinori
		and Sch{\"o}nherr, Roland
		and Heinemann, Stefan H.},
  title = 	{Impact of intracellular hemin on N-type inactivation of voltage-gated K + channels},
  journal = 	{Pfl{\"u}gers Archiv: European Journal of Physiology},
  year = 	{2020},
  month = 	{May},
  publisher = 	{Springer},
  address = 	{Berlin Heidelberg},
  volume = 	{472},
  number = 	{5},
  pages = 	{551--560},
  keywords = 	{K          +          channel inactivation; A-type channel; $\beta$ subunit; Hemin; Heme; Patch clamp},
  abstract = 	{N-type inactivation of voltage-gated K + channels is conferred by the N-terminal ``ball'' domains of select pore-forming $\alpha$ subunits or of auxiliary $\beta$ subunits, and influences electrical cellular excitability. Here, we show that hemin impairs inactivation of K + channels formed by Kv3.4 $\alpha$ subunits as well as that induced by the subunits Kv$\beta$1.1, Kv$\beta$1.2, and Kv$\beta$3.1 when coexpressed with $\alpha$ subunits of the Kv1 subfamily. In Kv$\beta$1.1, 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 $\alpha$ and auxiliary $\beta$ subunits. Free intracellular heme therefore has the potential to regulate cellular excitability via modulation of Kv channel inactivation.},
  note = 	{Zweitver{\"o}ffentlichung},
  issn = 	{0031-6768},
  doi = 	{10.1007/s00424-020-02386-1},
  url = 	{https://www.db-thueringen.de/receive/dbt_mods_00057185},
  url = 	{https://doi.org/10.1007/s00424-020-02386-1},
  file = 	{:https://www.db-thueringen.de/servlets/MCRFileNodeServlet/dbt_derivate_00060111/s00424-020-02386-1.pdf:PDF},
  language = 	{en}
}