Mechanism of external K+ sensitivity of KCNQ1 channels.
Journal
The Journal of general physiology
ISSN: 1540-7748
Titre abrégé: J Gen Physiol
Pays: United States
ID NLM: 2985110R
Informations de publication
Date de publication:
01 05 2023
01 05 2023
Historique:
received:
31
05
2022
revised:
20
12
2022
accepted:
31
01
2023
entrez:
22
2
2023
pubmed:
23
2
2023
medline:
25
2
2023
Statut:
ppublish
Résumé
KCNQ1 voltage-gated K+ channels are involved in a wide variety of fundamental physiological processes and exhibit the unique feature of being markedly inhibited by external K+. Despite the potential role of this regulatory mechanism in distinct physiological and pathological processes, its exact underpinnings are not well understood. In this study, using extensive mutagenesis, molecular dynamics simulations, and single-channel recordings, we delineate the molecular mechanism of KCNQ1 modulation by external K+. First, we demonstrate the involvement of the selectivity filter in the external K+ sensitivity of the channel. Then, we show that external K+ binds to the vacant outermost ion coordination site of the selectivity filter inducing a diminution in the unitary conductance of the channel. The larger reduction in the unitary conductance compared to whole-cell currents suggests an additional modulatory effect of external K+ on the channel. Further, we show that the external K+ sensitivity of the heteromeric KCNQ1/KCNE complexes depends on the type of associated KCNE subunits.
Identifiants
pubmed: 36809486
pii: 213880
doi: 10.1085/jgp.202213205
pmc: PMC9960071
pii:
doi:
Substances chimiques
KCNQ1 Potassium Channel
0
Potassium Channels, Voltage-Gated
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CIHR
ID : PJT-156181
Pays : Canada
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023 Abrahamyan et al.
Références
Arch Otorhinolaryngol. 1979;224(1-2):25-30
pubmed: 485945
Hear Res. 2001 Mar;153(1-2):132-45
pubmed: 11223304
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18922-7
pubmed: 24190995
Proc Natl Acad Sci U S A. 2015 May 5;112(18):5714-9
pubmed: 25901329
J Comput Chem. 2005 Dec;26(16):1701-18
pubmed: 16211538
Science. 2014 Oct 17;346(6207):352-5
pubmed: 25324389
Sci Adv. 2022 Mar 18;8(11):eabm7814
pubmed: 35302848
J Chem Theory Comput. 2008 Mar;4(3):435-47
pubmed: 26620784
Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14628-33
pubmed: 19667202
Am J Physiol. 1990 Apr;258(4 Pt 2):H1200-7
pubmed: 2331008
J Gen Physiol. 2018 Oct 1;150(10):1408-1420
pubmed: 30072373
Elife. 2016 Jan 23;5:
pubmed: 26802629
J Biol Chem. 2008 Jul 11;283(28):19448-55
pubmed: 18474599
Biophys J. 1998 Aug;75(2):785-92
pubmed: 9675180
J Gen Physiol. 1997 Jun;109(6):779-89
pubmed: 9222903
J Gen Physiol. 2008 Jun;131(6):589-603
pubmed: 18504315
Am J Physiol. 1994 Sep;267(3 Pt 1):C857-64
pubmed: 7943212
Biophys J. 2011 Feb 16;100(4):885-94
pubmed: 21320432
J Cell Physiol. 2010 Nov;225(3):692-700
pubmed: 20533308
J Gen Physiol. 2014 Sep;144(3):221-30
pubmed: 25156116
Biophys J. 2000 Jan;78(1):211-26
pubmed: 10620287
Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):E996-1005
pubmed: 23431135
Circ Res. 2006 Apr 28;98(8):1055-63
pubmed: 16556865
Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):743-8
pubmed: 19131515
Physiology (Bethesda). 2006 Oct;21:336-45
pubmed: 16990454
Cell. 2017 Jun 1;169(6):1042-1050.e9
pubmed: 28575668
Circulation. 1998 Jan 20;97(2):142-6
pubmed: 9445165
Biophys J. 1998 Apr;74(4):1840-9
pubmed: 9545046
J Physiol. 1998 Jul 1;510 ( Pt 1):37-45
pubmed: 9625865
Nat Commun. 2017 Nov 23;8(1):1730
pubmed: 29167462
J Gen Physiol. 1998 Dec;112(6):651-63
pubmed: 9834138
Diabetes. 2014 Apr;63(4):1315-25
pubmed: 24357532
J Chem Theory Comput. 2015 Apr 14;11(4):1864-74
pubmed: 26574392
Prog Biophys Mol Biol. 2006 Oct;92(2):185-208
pubmed: 16316679
J Chem Theory Comput. 2015 Aug 11;11(8):3696-713
pubmed: 26574453
Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):15096-100
pubmed: 26598654
Nat Chem. 2018 Aug;10(8):813-820
pubmed: 30030538
Front Physiol. 2020 Jun 04;11:504
pubmed: 32581825
Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697
pubmed: 9895674
J Phys Chem B. 2008 Jul 31;112(30):9020-41
pubmed: 18593145
Biophys J. 2011 Aug 17;101(4):818-27
pubmed: 21843472
Cell. 2020 Jan 23;180(2):340-347.e9
pubmed: 31883792
Nature. 2010 Jul 8;466(7303):203-8
pubmed: 20613835
Biochim Biophys Acta. 2016 Jul;1858(7 Pt B):1741-52
pubmed: 26874204
Circ Res. 2006 Apr 28;98(8):1048-54
pubmed: 16556866
Biophys J. 2000 Jun;78(6):2900-17
pubmed: 10827971
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1751-6
pubmed: 18218777
J Mol Biol. 2021 Aug 20;433(17):167002
pubmed: 33891905
J Gen Physiol. 2015 Mar;145(3):201-12
pubmed: 25712016
Cell Signal. 2015 Jul;27(7):1457-68
pubmed: 25892084
EMBO J. 2000 Dec 1;19(23):6326-30
pubmed: 11101505
Nature. 1996 Nov 7;384(6604):80-3
pubmed: 8900283
Structure. 2014 Nov 4;22(11):1582-94
pubmed: 25441029
J Physiol. 1990 Feb;421:135-50
pubmed: 2161457
J Comput Chem. 2008 Aug;29(11):1859-65
pubmed: 18351591
J Biol Chem. 2010 Mar 5;285(10):7165-75
pubmed: 20051516
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2466-70
pubmed: 1549610
Hear Res. 1987;29(2-3):117-24
pubmed: 3040655
Pflugers Arch. 1987 Dec;410(6):596-603
pubmed: 3449799
J Gen Physiol. 2018 Jan 2;150(1):7-18
pubmed: 29233885
Physiology (Bethesda). 2005 Dec;20:408-16
pubmed: 16287990
Nature. 2000 Jan 13;403(6766):196-9
pubmed: 10646604
Biophys J. 2009 Jul 8;97(1):50-8
pubmed: 19580743
Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):13180-5
pubmed: 23861489
Circ Res. 2010 Apr 2;106(6):1072-82
pubmed: 20133899
J Gen Physiol. 2021 Sep 6;153(9):
pubmed: 34357375
Biophys J. 2008 Sep 15;95(6):2759-78
pubmed: 18567635
Nat Commun. 2017 Nov 3;8(1):1289
pubmed: 29097701
J Gen Physiol. 1998 Dec;112(6):665-78
pubmed: 9834139
Nat Commun. 2019 Nov 26;10(1):5366
pubmed: 31772184
Sci Transl Med. 2009 Oct 14;1(2):2ra6
pubmed: 20368164
PLoS Comput Biol. 2013;9(5):e1003058
pubmed: 23658510
N Engl J Med. 2004 Oct 7;351(15):1548-63
pubmed: 15470219
Biochim Biophys Acta. 1999 Oct 15;1421(2):213-33
pubmed: 10518693
Nature. 2001 Nov 1;414(6859):43-8
pubmed: 11689936
J Physiol. 2008 Apr 1;586(7):1785-9
pubmed: 18174212
Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5833-8
pubmed: 20231479
J Physiol. 2006 Oct 1;576(Pt 1):73-86
pubmed: 16901941
Nat Genet. 1996 Jan;12(1):17-23
pubmed: 8528244
J Gen Physiol. 2019 Oct 7;151(10):1231-1246
pubmed: 31511304
Gastroenterology. 1994 Aug;107(2):548-71
pubmed: 8039632
Nat Struct Mol Biol. 2017 Oct;24(10):857-865
pubmed: 28846092
Chem Rev. 2019 Jul 10;119(13):7737-7832
pubmed: 31246417
Biophys J. 2011 Aug 17;101(4):809-17
pubmed: 21843471
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18862-7
pubmed: 20962273
J Gen Physiol. 2012 Dec;140(6):653-69
pubmed: 23183700
J Biol Chem. 1996 Jul 19;271(29):17261-6
pubmed: 8663367
Hum Mutat. 2009 Nov;30(11):1486-511
pubmed: 19862833
Pediatr Emerg Care. 2008 Mar;24(3):157-60
pubmed: 18347493
EMBO J. 2003 Oct 15;22(20):5412-21
pubmed: 14532114
J Physiol. 2011 Dec 15;589(Pt 24):5949-63
pubmed: 22025665
Nature. 1996 Nov 7;384(6604):78-80
pubmed: 8900282
EMBO J. 2009 Sep 16;28(18):2825-34
pubmed: 19661921
EMBO J. 1997 Sep 1;16(17):5472-9
pubmed: 9312006
J Physiol. 2015 Jun 15;593(12):2605-15
pubmed: 25653179
Recept Channels. 1993;1(1):61-71
pubmed: 8081712