Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase α2-Isoform

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase α2-Isoform. / Rajanathan, Rajkumar; Riera, Clàudia Vilaseca i.; Pedersen, Tina Myhre; Staehr, Christian; Bouzinova, Elena V.; Nyengaard, Jens Randel; Thomsen, Morten B.; Bøtker, Hans Erik; Matchkov, Vladimir V.

In: Cells, Vol. 12, No. 8, 1108, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rajanathan, R, Riera, CVI, Pedersen, TM, Staehr, C, Bouzinova, EV, Nyengaard, JR, Thomsen, MB, Bøtker, HE & Matchkov, VV 2023, 'Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase α2-Isoform', Cells, vol. 12, no. 8, 1108. https://doi.org/10.3390/cells12081108

APA

Rajanathan, R., Riera, C. V. I., Pedersen, T. M., Staehr, C., Bouzinova, E. V., Nyengaard, J. R., Thomsen, M. B., Bøtker, H. E., & Matchkov, V. V. (2023). Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase α2-Isoform. Cells, 12(8), [1108]. https://doi.org/10.3390/cells12081108

Vancouver

Rajanathan R, Riera CVI, Pedersen TM, Staehr C, Bouzinova EV, Nyengaard JR et al. Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase α2-Isoform. Cells. 2023;12(8). 1108. https://doi.org/10.3390/cells12081108

Author

Rajanathan, Rajkumar ; Riera, Clàudia Vilaseca i. ; Pedersen, Tina Myhre ; Staehr, Christian ; Bouzinova, Elena V. ; Nyengaard, Jens Randel ; Thomsen, Morten B. ; Bøtker, Hans Erik ; Matchkov, Vladimir V. / Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase α2-Isoform. In: Cells. 2023 ; Vol. 12, No. 8.

Bibtex

@article{43129e8e5ab149339fe4d3a79d223eae,
title = "Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase α2-Isoform",
abstract = "Two α-isoforms of the Na+,K+-ATPase (α1 and α2) are expressed in the cardiovascular system, and it is unclear which isoform is the preferential regulator of contractility. Mice heterozygous for the familial hemiplegic migraine type 2 (FHM2) associated mutation in the α2-isoform (G301R; α2+/G301R mice) have decreased expression of cardiac α2-isoform but elevated expression of the α1-isoform. We aimed to investigate the contribution of the α2-isoform function to the cardiac phenotype of α2+/G301R hearts. We hypothesized that α2+/G301R hearts exhibit greater contractility due to reduced expression of cardiac α2-isoform. Variables for contractility and relaxation of isolated hearts were assessed in the Langendorff system without and in the presence of ouabain (1 µM). Atrial pacing was performed to investigate rate-dependent changes. The α2+/G301R hearts displayed greater contractility than WT hearts during sinus rhythm, which was rate-dependent. The inotropic effect of ouabain was more augmented in α2+/G301R hearts than in WT hearts during sinus rhythm and atrial pacing. In conclusion, cardiac contractility was greater in α2+/G301R hearts than in WT hearts under resting conditions. The inotropic effect of ouabain was rate-independent and enhanced in α2+/G301R hearts, which was associated with increased systolic work.",
keywords = "cardiac function, cardiovascular, contractility, familial hemiplegic migraine, Langendorff, Na,K-ATPase, ouabain, perfusion, relaxation, α-isoform",
author = "Rajkumar Rajanathan and Riera, {Cl{\`a}udia Vilaseca i.} and Pedersen, {Tina Myhre} and Christian Staehr and Bouzinova, {Elena V.} and Nyengaard, {Jens Randel} and Thomsen, {Morten B.} and B{\o}tker, {Hans Erik} and Matchkov, {Vladimir V.}",
note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",
year = "2023",
doi = "10.3390/cells12081108",
language = "English",
volume = "12",
journal = "Cells",
issn = "2073-4409",
publisher = "MDPI AG",
number = "8",

}

RIS

TY - JOUR

T1 - Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase α2-Isoform

AU - Rajanathan, Rajkumar

AU - Riera, Clàudia Vilaseca i.

AU - Pedersen, Tina Myhre

AU - Staehr, Christian

AU - Bouzinova, Elena V.

AU - Nyengaard, Jens Randel

AU - Thomsen, Morten B.

AU - Bøtker, Hans Erik

AU - Matchkov, Vladimir V.

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - Two α-isoforms of the Na+,K+-ATPase (α1 and α2) are expressed in the cardiovascular system, and it is unclear which isoform is the preferential regulator of contractility. Mice heterozygous for the familial hemiplegic migraine type 2 (FHM2) associated mutation in the α2-isoform (G301R; α2+/G301R mice) have decreased expression of cardiac α2-isoform but elevated expression of the α1-isoform. We aimed to investigate the contribution of the α2-isoform function to the cardiac phenotype of α2+/G301R hearts. We hypothesized that α2+/G301R hearts exhibit greater contractility due to reduced expression of cardiac α2-isoform. Variables for contractility and relaxation of isolated hearts were assessed in the Langendorff system without and in the presence of ouabain (1 µM). Atrial pacing was performed to investigate rate-dependent changes. The α2+/G301R hearts displayed greater contractility than WT hearts during sinus rhythm, which was rate-dependent. The inotropic effect of ouabain was more augmented in α2+/G301R hearts than in WT hearts during sinus rhythm and atrial pacing. In conclusion, cardiac contractility was greater in α2+/G301R hearts than in WT hearts under resting conditions. The inotropic effect of ouabain was rate-independent and enhanced in α2+/G301R hearts, which was associated with increased systolic work.

AB - Two α-isoforms of the Na+,K+-ATPase (α1 and α2) are expressed in the cardiovascular system, and it is unclear which isoform is the preferential regulator of contractility. Mice heterozygous for the familial hemiplegic migraine type 2 (FHM2) associated mutation in the α2-isoform (G301R; α2+/G301R mice) have decreased expression of cardiac α2-isoform but elevated expression of the α1-isoform. We aimed to investigate the contribution of the α2-isoform function to the cardiac phenotype of α2+/G301R hearts. We hypothesized that α2+/G301R hearts exhibit greater contractility due to reduced expression of cardiac α2-isoform. Variables for contractility and relaxation of isolated hearts were assessed in the Langendorff system without and in the presence of ouabain (1 µM). Atrial pacing was performed to investigate rate-dependent changes. The α2+/G301R hearts displayed greater contractility than WT hearts during sinus rhythm, which was rate-dependent. The inotropic effect of ouabain was more augmented in α2+/G301R hearts than in WT hearts during sinus rhythm and atrial pacing. In conclusion, cardiac contractility was greater in α2+/G301R hearts than in WT hearts under resting conditions. The inotropic effect of ouabain was rate-independent and enhanced in α2+/G301R hearts, which was associated with increased systolic work.

KW - cardiac function

KW - cardiovascular

KW - contractility

KW - familial hemiplegic migraine

KW - Langendorff

KW - Na,K-ATPase

KW - ouabain

KW - perfusion

KW - relaxation

KW - α-isoform

UR - http://www.scopus.com/inward/record.url?scp=85156255616&partnerID=8YFLogxK

U2 - 10.3390/cells12081108

DO - 10.3390/cells12081108

M3 - Journal article

C2 - 37190017

AN - SCOPUS:85156255616

VL - 12

JO - Cells

JF - Cells

SN - 2073-4409

IS - 8

M1 - 1108

ER -

ID: 347002657