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Pflugers Arch
2020 May 01;4725:551-560. doi: 10.1007/s00424-020-02386-1.
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Impact of intracellular hemin on N-type inactivation of voltage-gated K+ channels.
Coburger I
,
Yang K
,
Bernert A
,
Wiesel E
,
Sahoo N
,
Swain SM
,
Hoshi T
,
Schönherr R
,
Heinemann SH
.
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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.
Antz,
NMR structure of inactivation gates from mammalian voltage-dependent potassium channels.
1997, Pubmed
Antz,
NMR structure of inactivation gates from mammalian voltage-dependent potassium channels.
1997,
Pubmed
Atamna,
Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging.
2002,
Pubmed
Barry,
Differential expression of voltage-gated K+ channel subunits in adult rat heart. Relation to functional K+ channels?
1995,
Pubmed
Beck,
Interactions between multiple phosphorylation sites in the inactivation particle of a K+ channel. Insights into the molecular mechanism of protein kinase C action.
1998,
Pubmed
,
Xenbase
Cai,
Multiple modes of a-type potassium current regulation.
2007,
Pubmed
Covarrubias,
Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate.
1994,
Pubmed
,
Xenbase
Dixon,
Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats.
1994,
Pubmed
Giese,
Reduced K+ channel inactivation, spike broadening, and after-hyperpolarization in Kvbeta1.1-deficient mice with impaired learning.
1998,
Pubmed
Heinemann,
Functional characterization of Kv channel beta-subunits from rat brain.
1996,
Pubmed
,
Xenbase
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase
Jerng,
Modulatory mechanisms and multiple functions of somatodendritic A-type K (+) channel auxiliary subunits.
2014,
Pubmed
Jow,
Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvbeta1.1 A-type K+ channels.
2004,
Pubmed
,
Xenbase
Kaprielian,
Relationship between K+ channel down-regulation and [Ca2+]i in rat ventricular myocytes following myocardial infarction.
1999,
Pubmed
Kühl,
Regulatory Fe(II/III) heme: the reconstruction of a molecule's biography.
2014,
Pubmed
Lee,
Downregulation of voltage-gated K(+) channels in rat heart with right ventricular hypertrophy.
1999,
Pubmed
Liu,
Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.
2017,
Pubmed
Lu,
Disruption of Kv1.1 N-type inactivation by novel small molecule inhibitors (disinactivators).
2008,
Pubmed
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
Mense,
Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases.
2006,
Pubmed
Nishiyama,
Altered K(+) channel gene expression in diabetic rat ventricle: isoform switching between Kv4.2 and Kv1.4.
2001,
Pubmed
Ogawa,
Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1.
2001,
Pubmed
,
Xenbase
Ogielska,
Cooperative subunit interactions in C-type inactivation of K channels.
1995,
Pubmed
,
Xenbase
Oliver,
Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.
2004,
Pubmed
,
Xenbase
Padanilam,
Molecular determinants of intracellular pH modulation of human Kv1.4 N-type inactivation.
2002,
Pubmed
,
Xenbase
Pardo,
Extracellular K+ specifically modulates a rat brain K+ channel.
1992,
Pubmed
,
Xenbase
Rettig,
Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
1994,
Pubmed
,
Xenbase
Ritter,
Dysregulation of Kv3.4 channels in dorsal root ganglia following spinal cord injury.
2015,
Pubmed
Ritter,
Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons.
2012,
Pubmed
Roeper,
Frequency-dependent inactivation of mammalian A-type K+ channel KV1.4 regulated by Ca2+/calmodulin-dependent protein kinase.
1997,
Pubmed
Ruppersberg,
Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation.
1991,
Pubmed
,
Xenbase
Sahoo,
Cysteines control the N- and C-linker-dependent gating of KCNH1 potassium channels.
2012,
Pubmed
,
Xenbase
Sahoo,
Heme impairs the ball-and-chain inactivation of potassium channels.
2013,
Pubmed
,
Xenbase
Sheng,
Subcellular segregation of two A-type K+ channel proteins in rat central neurons.
1992,
Pubmed
,
Xenbase
Shimizu,
Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres.
2019,
Pubmed
Tang,
Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels.
2003,
Pubmed
Wissmann,
Solution structure and function of the "tandem inactivation domain" of the neuronal A-type potassium channel Kv1.4.
2003,
Pubmed
Yang,
Modulation of K+ channel N-type inactivation by sulfhydration through hydrogen sulfide and polysulfides.
2019,
Pubmed
