{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(8)"],"submitter":["Rajanathan R"],"pubmed_abstract":["Two α-isoforms of the Na<sup>+</sup>,K<sup>+</sup>-ATPase (α<sub>1</sub> and α<sub>2</sub>) 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 α<sub>2</sub>-isoform (G301R; α<sub>2</sub><sup>+/G301R</sup> mice) have decreased expression of cardiac α<sub>2</sub>-isoform but elevated expression of the α<sub>1</sub>-isoform. We aimed to investigate the contribution of the α<sub>2</sub>-isoform function to the cardiac phenotype of α<sub>2</sub><sup>+/G301R</sup> hearts. We hypothesized that α<sub>2</sub><sup>+/G301R</sup> hearts exhibit greater contractility due to reduced expression of cardiac α<sub>2</sub>-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 α<sub>2</sub><sup>+/G301R</sup> hearts displayed greater contractility than WT hearts during sinus rhythm, which was rate-dependent. The inotropic effect of ouabain was more augmented in α<sub>2</sub><sup>+/G301R</sup> hearts than in WT hearts during sinus rhythm and atrial pacing. In conclusion, cardiac contractility was greater in α<sub>2</sub><sup>+/G301R</sup> hearts than in WT hearts under resting conditions. The inotropic effect of ouabain was rate-independent and enhanced in α<sub>2</sub><sup>+/G301R</sup> hearts, which was associated with increased systolic work."],"journal":["Cells"],"pagination":["1108"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10136638"],"repository":["biostudies-literature"],"pubmed_title":["Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>,K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform."],"pmcid":["PMC10136638"],"pubmed_authors":["Rajanathan R","Pedersen TM","Thomsen MB","Matchkov VV","Riera CVI","Staehr C","Botker HE","Nyengaard JR","Bouzinova EV"],"additional_accession":[]},"is_claimable":false,"name":"Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na<sup>+</sup>,K<sup>+</sup>-ATPase α<sub>2</sub>-Isoform.","description":"Two α-isoforms of the Na<sup>+</sup>,K<sup>+</sup>-ATPase (α<sub>1</sub> and α<sub>2</sub>) 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 α<sub>2</sub>-isoform (G301R; α<sub>2</sub><sup>+/G301R</sup> mice) have decreased expression of cardiac α<sub>2</sub>-isoform but elevated expression of the α<sub>1</sub>-isoform. We aimed to investigate the contribution of the α<sub>2</sub>-isoform function to the cardiac phenotype of α<sub>2</sub><sup>+/G301R</sup> hearts. We hypothesized that α<sub>2</sub><sup>+/G301R</sup> hearts exhibit greater contractility due to reduced expression of cardiac α<sub>2</sub>-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 α<sub>2</sub><sup>+/G301R</sup> hearts displayed greater contractility than WT hearts during sinus rhythm, which was rate-dependent. The inotropic effect of ouabain was more augmented in α<sub>2</sub><sup>+/G301R</sup> hearts than in WT hearts during sinus rhythm and atrial pacing. In conclusion, cardiac contractility was greater in α<sub>2</sub><sup>+/G301R</sup> hearts than in WT hearts under resting conditions. The inotropic effect of ouabain was rate-independent and enhanced in α<sub>2</sub><sup>+/G301R</sup> hearts, which was associated with increased systolic work.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2025-04-22T05:14:44.357Z","creation":"2025-04-05T21:14:04.439Z"},"accession":"S-EPMC10136638","cross_references":{"pubmed":["37190017"],"doi":["10.3390/cells12081108"]}}