Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
Department of Basic Science, School of Medicine and Health Sciences, International University of Catalonia, 08195 Barcelona, Spain.
Cells. 2023 Apr 7;12(8):1108. doi: 10.3390/cells12081108.
Two α-isoforms of the Na,K-ATPase (α and α) 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-isoform (G301R; α mice) have decreased expression of cardiac α-isoform but elevated expression of the α-isoform. We aimed to investigate the contribution of the α-isoform function to the cardiac phenotype of α hearts. We hypothesized that α hearts exhibit greater contractility due to reduced expression of cardiac α-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 hearts displayed greater contractility than WT hearts during sinus rhythm, which was rate-dependent. The inotropic effect of ouabain was more augmented in α hearts than in WT hearts during sinus rhythm and atrial pacing. In conclusion, cardiac contractility was greater in α hearts than in WT hearts under resting conditions. The inotropic effect of ouabain was rate-independent and enhanced in α hearts, which was associated with increased systolic work.
两种α-钠钾 ATP 酶同工型（α和α）在心血管系统中表达，目前尚不清楚哪种同工型是收缩性的优先调节者。杂合子携带家族性偏瘫性偏头痛 2 型（FHM2）相关突变的α-同工型（G301R；α 小鼠）的心脏α-同工型表达降低，但α-同工型表达升高。我们旨在研究α-同工型功能对α 心脏心脏表型的贡献。我们假设α 心脏由于心脏α-同工型表达减少而表现出更大的收缩性。在 Langendorff 系统中，不使用和使用哇巴因（1µM）评估分离心脏的收缩性和舒张性变量。进行心房起搏以研究频率依赖性变化。α 心脏在窦性节律下的收缩性比 WT 心脏更强，这是频率依赖性的。在窦性节律和心房起搏下，哇巴因的变力作用在α 心脏中比在 WT 心脏中增强得更多。总之，在静息状态下，α 心脏的收缩性比 WT 心脏更强。哇巴因的变力作用与收缩做功增加有关，是独立于频率的，并在α 心脏中增强。
