Ryanodine receptor subtypes regulate Ca2+ sparks/spontaneous transient outward currents and myogenic tone of uterine arteries in pregnancy.
Adaptation, Physiological
Animals
Arterial Pressure
Calcium
/ metabolism
Calcium Signaling
Female
Gene Expression Regulation
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
/ genetics
Large-Conductance Calcium-Activated Potassium Channel beta Subunits
/ genetics
Pregnancy
Ryanodine Receptor Calcium Release Channel
/ genetics
Sheep, Domestic
Tissue Culture Techniques
Uterine Artery
/ metabolism
Vasoconstriction
Ca2+ sparks
Large-conductance Ca2+-activated K+
Myogenic tone
Pregnancy
Ryanodine receptor
Spontaneous transient outward currents
Uterine arteries
channel
Journal
Cardiovascular research
ISSN: 1755-3245
Titre abrégé: Cardiovasc Res
Pays: England
ID NLM: 0077427
Informations de publication
Date de publication:
22 02 2021
22 02 2021
Historique:
received:
21
08
2019
revised:
18
02
2020
accepted:
31
03
2020
pubmed:
7
4
2020
medline:
5
1
2022
entrez:
7
4
2020
Statut:
ppublish
Résumé
Our recent study demonstrated that increased Ca2+ sparks and spontaneous transient outward currents (STOCs) played an important role in uterine vascular tone and haemodynamic adaptation to pregnancy. The present study examined the role of ryanodine receptor (RyR) subtypes in regulating Ca2+ sparks/STOCs and myogenic tone in uterine arterial adaptation to pregnancy. Uterine arteries isolated from non-pregnant and near-term pregnant sheep were used in the present study. Pregnancy increased the association of α and β1 subunits of large-conductance Ca2+-activated K+ (BKCa) channels and enhanced the co-localization of RyR1 and RyR2 with the β1 subunit in the uterine artery. In contrast, RyR3 was not co-localized with BKCa β1 subunit. Knockdown of RyR1 or RyR2 in uterine arteries of pregnant sheep downregulated the β1 but not α subunit of the BKCa channel and decreased the association of α and β1 subunits. Unlike RyR1 and RyR2, knockdown of RyR3 had no significant effect on either expression or association of BKCa subunits. In addition, knockdown of RyR1 or RyR2 significantly decreased Ca2+ spark frequency, suppressed STOCs frequency and amplitude, and increased pressure-dependent myogenic tone in uterine arteries of pregnant animals. RyR3 knockdown did not affect Ca2+ sparks/STOCs and myogenic tone in the uterine artery. Together, the present study demonstrates a novel mechanistic paradigm of RyR subtypes in the regulation of Ca2+ sparks/STOCs and uterine vascular tone, providing new insights into the mechanisms underlying uterine vascular adaptation to pregnancy.
Identifiants
pubmed: 32251501
pii: 5816596
doi: 10.1093/cvr/cvaa089
pmc: PMC7898951
doi:
Substances chimiques
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
0
Large-Conductance Calcium-Activated Potassium Channel beta Subunits
0
Ryanodine Receptor Calcium Release Channel
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
792-804Subventions
Organisme : NICHD NIH HHS
ID : P01 HD083132
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128209
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137649
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149608
Pays : United States
Informations de copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
Références
J Biomed Biotechnol. 2009;2009:135249
pubmed: 20029633
Circ Res. 2007 Aug 31;101(5):493-502
pubmed: 17641230
J Biol Chem. 2001 Apr 6;276(14):11257-64
pubmed: 11150292
J Physiol. 2012 Jun 1;590(11):2709-20
pubmed: 22508960
Nat Rev Genet. 2012 Mar 13;13(4):227-32
pubmed: 22411467
Science. 1992 Apr 24;256(5056):532-5
pubmed: 1373909
Drug Discov Today. 2012 Sep;17(17-18):974-87
pubmed: 22521666
Sci Signal. 2017 Sep 19;10(497):
pubmed: 28928237
J Soc Gynecol Investig. 2005 Sep;12(6):402-8
pubmed: 15979352
Arterioscler Thromb Vasc Biol. 2005 May;25(5):932-43
pubmed: 15731494
Am J Physiol Heart Circ Physiol. 2015 Dec 1;309(11):H1915-22
pubmed: 26408536
Cell Calcium. 2008 Aug;44(2):190-201
pubmed: 18191199
Am J Physiol Cell Physiol. 2001 Dec;281(6):C1769-75
pubmed: 11698234
Physiology (Bethesda). 2006 Feb;21:69-78
pubmed: 16443824
Hypertension. 2017 Jul 24;:
pubmed: 28739977
Sci Signal. 2017 May 09;10(478):
pubmed: 28487419
Circ Res. 2001 Nov 23;89(11):1051-7
pubmed: 11717163
J Pharmacol Sci. 2004 Apr;94(4):339-47
pubmed: 15107573
Nature. 2000 Oct 19;407(6806):870-6
pubmed: 11057658
J Gen Physiol. 2004 Apr;123(4):377-86
pubmed: 15024040
Am J Physiol Cell Physiol. 2000 Feb;278(2):C235-56
pubmed: 10666018
Hypertension. 2019 Mar;73(3):691-702
pubmed: 30661479
Circ Res. 2014 Sep 12;115(7):650-61
pubmed: 25085940
J Biol Chem. 2000 Mar 31;275(13):9596-603
pubmed: 10734110
Mol Psychiatry. 2014 Dec;19(12):1295-304
pubmed: 25070539
Science. 1995 Oct 27;270(5236):633-7
pubmed: 7570021
Sci Signal. 2016 Oct 11;9(449):ra100
pubmed: 27729550
Cell. 2016 Apr 21;165(3):535-50
pubmed: 27104977
Am J Physiol Cell Physiol. 2010 Aug;299(2):C264-78
pubmed: 20445169
J Biol Chem. 2007 Feb 2;282(5):3231-40
pubmed: 17148444
J Gen Physiol. 2011 Aug;138(2):195-209
pubmed: 21746845
Hypertension. 2017 Jun;69(6):1181-1191
pubmed: 28396535
Hypertension. 2010 Oct;56(4):750-7
pubmed: 20660818
J Cell Sci. 2007 Nov 1;120(Pt 21):3784-91
pubmed: 17925380
Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):E9745-E9752
pubmed: 30181262
Nucleic Acids Res. 2001 May 1;29(9):e45
pubmed: 11328886
Circ Res. 2000 Nov 24;87(11):E53-60
pubmed: 11090555
J Gen Physiol. 2000 Sep;116(3):411-32
pubmed: 10962017
Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1878-87
pubmed: 19470517
Neuron. 2008 Sep 25;59(6):873-81
pubmed: 18817728
Am J Physiol Cell Physiol. 2018 Jul 1;315(1):C1-C9
pubmed: 29537866
J Appl Physiol (1985). 2001 Sep;91(3):1350-4
pubmed: 11509535
J Gen Physiol. 1999 Feb;113(2):229-38
pubmed: 9925821
Int J Mol Sci. 2017 Jun 24;18(7):
pubmed: 28672801
J Cell Sci. 2004 Dec 1;117(Pt 25):6175-83
pubmed: 15564379
Hypertension. 2011 Dec;58(6):1132-9
pubmed: 22042813
Cell Calcium. 2006 Nov-Dec;40(5-6):461-93
pubmed: 17069885
J Biol Chem. 2002 Oct 4;277(40):37756-64
pubmed: 12145283
Physiol Rev. 2018 Jul 1;98(3):1241-1334
pubmed: 29717932
Hypertension. 2014 Sep;64(3):610-8
pubmed: 24914190
Biochim Biophys Acta. 2009 Jun;1793(6):1096-104
pubmed: 19250948
J Physiol. 1998 Apr 1;508 ( Pt 1):211-21
pubmed: 9490841
Am J Physiol Heart Circ Physiol. 2000 Jul;279(1):H319-28
pubmed: 10899072
Nature. 2011 May 19;473(7347):337-42
pubmed: 21593866
J Am Heart Assoc. 2019 May 7;8(9):e010090
pubmed: 31030596
Am J Physiol Lung Cell Mol Physiol. 2005 Aug;289(2):L338-48
pubmed: 15863441