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- Title
Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na + ,K + -ATPase α 2 -Isoform.
- Authors
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.
- 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.
- Subjects
HEART; MIGRAINE aura; PHENOTYPES; CARDIOVASCULAR system; OUABAIN
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 8, p1108
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12081108