| First Author | Cellini A | Year | 2021 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 321 |
| Issue | 4 | Pages | H650-H662 |
| PubMed ID | 34448639 | Mgi Jnum | J:310928 |
| Mgi Id | MGI:6762524 | Doi | 10.1152/ajpheart.00808.2020 |
| Citation | Cellini A, et al. (2021) The alpha2-isoform of the Na(+)/K(+)-ATPase protects against pathological remodeling and beta-adrenergic desensitization after myocardial infarction. Am J Physiol Heart Circ Physiol 321(4):H650-H662 |
| abstractText | The role of the Na(+)/K(+)-ATPase (NKA) in heart failure associated with myocardial infarction (MI) is poorly understood. The elucidation of its precise function is hampered by the existence of two catalytic NKA isoforms (NKA-alpha1 and NKA-alpha2). Our aim was to analyze the effects of an increased NKA-alpha2 expression on functional deterioration and remodeling during long-term MI treatment in mice and its impact on Ca(2+) handling and inotropy of the failing heart. Wild-type (WT) and NKA-alpha2 transgenic (TG) mice (TG-alpha2) with a cardiac-specific overexpression of NKA-alpha2 were subjected to MI injury for 8 wk. As examined by echocardiography, gravimetry, and histology, TG-alpha2 mice were protected from functional deterioration and adverse cardiac remodeling. Contractility and Ca(2+) transients (Fura 2-AM) in cardiomyocytes from MI-treated TG-alpha2 animals showed reduced Ca(2+) amplitudes during pacing or after caffeine application. Ca(2+) efflux in cardiomyocytes from TG-alpha2 mice was accelerated and diastolic Ca(2+) levels were decreased. Based on these alterations, sarcomeres exhibited an enhanced sensitization and thus increased contractility. After the acute stimulation with the beta-adrenergic agonist isoproterenol (ISO), cardiomyocytes from MI-treated TG-alpha2 mice responded with increased sarcomere shortenings and Ca(2+) peak amplitudes. This positive inotropic response was absent in cardiomyocytes from WT-MI animals. Cardiomyocytes with NKA-alpha2 as predominant isoform minimize Ca(2+) cycling but respond to beta-adrenergic stimulation more efficiently during chronic cardiac stress. These mechanisms might improve the beta-adrenergic reserve and contribute to functional preservation in heart failure.NEW & NOTEWORTHY Reduced systolic and diastolic calcium levels in cardiomyocytes from NKA-alpha2 transgenic mice minimize the desensitization of the beta-adrenergic signaling system. These effects result in an improved beta-adrenergic reserve and prevent functional deterioration and cardiac remodeling. |
