Nanoscale Organisation of Ryanodine Receptors and Junctophilin-2 in the Failing Human Heart.
collagen VI
fibrosis
junctophilin
ryanodine receptor
t-tubules
Journal
Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006
Informations de publication
Date de publication:
2021
2021
Historique:
received:
13
06
2021
accepted:
03
09
2021
entrez:
25
10
2021
pubmed:
26
10
2021
medline:
26
10
2021
Statut:
epublish
Résumé
The disrupted organisation of the ryanodine receptors (RyR) and junctophilin (JPH) is thought to underpin the transverse tubule (t-tubule) remodelling in a failing heart. Here, we assessed the nanoscale organisation of these two key proteins in the failing human heart. Recently, an advanced feature of the t-tubule remodelling identified large flattened t-tubules called t-sheets, that were several microns wide. Previously, we reported that in the failing heart, the dilated t-tubules up to ~1 μm wide had increased collagen, and we hypothesised that the t-sheets would also be associated with collagen deposits. Direct stochastic optical reconstruction microscopy (dSTORM), confocal microscopy, and western blotting were used to evaluate the cellular distribution of excitation-contraction structures in the cardiac myocytes from patients with idiopathic dilated cardiomyopathy (IDCM) compared to myocytes from the non-failing (NF) human heart. The dSTORM imaging of RyR and JPH found no difference in the colocalisation between IDCM and NF myocytes, but there was a higher colocalisation at the t-tubule and sarcolemma compared to the corbular regions. Western blots revealed no change in the JPH expression but did identify a ~50% downregulation of RyR (
Identifiants
pubmed: 34690801
doi: 10.3389/fphys.2021.724372
pmc: PMC8531480
doi:
Types de publication
Journal Article
Langues
eng
Pagination
724372Informations de copyright
Copyright © 2021 Hou, Bai, Shen, de Langen, Li, Lal, dos Remedios, Baddeley, Ruygrok, Soeller and Crossman.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Cardiovasc Res. 2017 Jul 1;113(8):879-891
pubmed: 28444133
PLoS One. 2011;6(10):e25100
pubmed: 22022376
J Mol Cell Cardiol. 2007 Jun;42(6):1026-35
pubmed: 17509612
Biophys J. 2012 Mar 7;102(5):L19-21
pubmed: 22404946
Expert Opin Biol Ther. 2010 Jan;10(1):29-41
pubmed: 20078230
Circ Res. 1979 Aug;45(2):260-7
pubmed: 376173
J Cell Sci. 2016 Dec 1;129(23):4388-4398
pubmed: 27802169
Nature. 2002 Jan 10;415(6868):198-205
pubmed: 11805843
J Biol Chem. 2015 Jul 17;290(29):17946-17955
pubmed: 26063807
Methods Mol Biol. 2017;1663:205-217
pubmed: 28924670
Heart Fail Rev. 2015 Mar;20(2):203-14
pubmed: 25112961
Eur Heart J. 2018 Jan 1;39(1):60-69
pubmed: 28549109
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):14958-63
pubmed: 17848521
Mol Cell. 2000 Jul;6(1):11-22
pubmed: 10949023
NPJ Aging Mech Dis. 2021 May 28;7(1):16
pubmed: 34050186
Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4305-10
pubmed: 16537526
ACS Nano. 2019 Feb 26;13(2):2143-2157
pubmed: 30715853
Circ Res. 2014 Dec 5;115(12):986-96
pubmed: 25332206
Cardiovasc Res. 2015 Dec 1;108(3):387-98
pubmed: 26490742
Biophys J. 2009 Nov 18;97(10):2664-73
pubmed: 19917219
Circ Res. 2008 Feb 15;102(3):338-46
pubmed: 18079411
Circulation. 1992 Mar;85(3):1046-55
pubmed: 1311223
Science. 1993 Oct 29;262(5134):740-4
pubmed: 8235594
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22275-80
pubmed: 20018773
J Physiol. 2006 Jul 15;574(Pt 2):519-33
pubmed: 16709642
Biophys J. 2010 Dec 15;99(12):3923-9
pubmed: 21156134
J Physiol. 2019 Jan;597(2):399-418
pubmed: 30412283
Prog Biophys Mol Biol. 2017 Nov;130(Pt B):302-314
pubmed: 28709857
Biochem Biophys Res Commun. 2004 Dec 17;325(3):852-6
pubmed: 15541368
Elife. 2018 Oct 30;7:
pubmed: 30375974
PLoS One. 2011;6(5):e20645
pubmed: 21655189
Circ Res. 2013 Nov 8;113(11):1219-30
pubmed: 24044951
Circ Res. 2000 Apr 28;86(8):846-53
pubmed: 10785506
Cardiovasc Res. 2014 Jul 15;103(2):198-205
pubmed: 24935431
J Mol Cell Cardiol. 2015 Jul;84:170-8
pubmed: 25953258
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15196-201
pubmed: 25288764
Basic Res Cardiol. 1997;92 Suppl 1:87-93
pubmed: 9202848
PLoS One. 2011 Mar 09;6(3):e17901
pubmed: 21408028
JACC Basic Transl Sci. 2018 Aug 28;3(4):503-517
pubmed: 30175274
J Am Coll Cardiol. 2021 Feb 2;77(4):405-419
pubmed: 33509397
Am J Physiol. 1999 Aug;277(2):H603-9
pubmed: 10444485
Circ Res. 2012 Feb 17;110(4):588-97
pubmed: 22253411
Nature. 1989 Mar 9;338(6211):167-70
pubmed: 2537473
Circ Res. 2010 Aug 20;107(4):520-31
pubmed: 20576937
J Am Heart Assoc. 2018 Jun 21;7(13):
pubmed: 29929992
Circulation. 2017 Apr 25;135(17):1632-1645
pubmed: 28073805
Biophys J. 1999 Sep;77(3):1528-39
pubmed: 10465763
Clin Exp Pharmacol Physiol. 2012 May;39(5):469-76
pubmed: 21790719
Circ Res. 1999 Feb 19;84(3):266-75
pubmed: 10024300
Circulation. 2011 Mar 8;123(9):979-88
pubmed: 21339484
Methods. 2015 Oct 15;88:98-108
pubmed: 25814438
Arch Histol Cytol. 2002 Jun;65(2):109-26
pubmed: 12164335
Nat Rev Dis Primers. 2019 May 9;5(1):32
pubmed: 31073128
Circ Heart Fail. 2015 Nov;8(6):1105-14
pubmed: 26294422
Pac Symp Biocomput. 2009;:328-39
pubmed: 19209712
Int J Cardiol. 2016 Dec 15;225:371-380
pubmed: 27760414
Cardiovasc Res. 2013 May 1;98(2):269-76
pubmed: 23405000