| First Author | Kutz LC | Year | 2018 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 314 |
| Issue | 6 | Pages | E620-E629 |
| PubMed ID | 29438630 | Mgi Jnum | J:273197 |
| Mgi Id | MGI:6283971 | Doi | 10.1152/ajpendo.00275.2017 |
| Citation | Kutz LC, et al. (2018) Isoform-specific role of Na/K-ATPase alpha1 in skeletal muscle. Am J Physiol Endocrinol Metab 314(6):E620-E629 |
| abstractText | The distribution of Na/K-ATPase alpha-isoforms in skeletal muscle is unique, with alpha1 as the minor (15%) isoform and alpha2 comprising the bulk of the Na/K-ATPase pool. The acute and isoform-specific role of alpha2 in muscle performance and resistance to fatigue is well known, but the isoform-specific role of alpha1 has not been as thoroughly investigated. In vitro, we reported that alpha1 has a role in promoting cell growth that is not supported by alpha2. To assess whether alpha1 serves this isoform-specific trophic role in the skeletal muscle, we used Na/K-ATPase alpha1-haploinsufficient (alpha1(+/-)) mice. A 30% decrease of Na/K-ATPase alpha1 protein expression without change in alpha2 induced a modest yet significant decrease of 10% weight in the oxidative soleus muscle. In contrast, the mixed plantaris and glycolytic extensor digitorum longus weights were not significantly affected, likely because of their very low expression level of alpha1 compared with the soleus. The soleus mass reduction occurred without change in total Na/K-ATPase activity or glycogen metabolism. Serum analytes including K(+), fat tissue mass, and exercise capacity were not altered in alpha1(+/-) mice. The impact of alpha1 content on soleus muscle mass is consistent with a Na/K-ATPase alpha1-specific role in skeletal muscle growth that cannot be fulfilled by alpha2. The preserved running capacity in alpha1(+/-) is in sharp contrast with previously reported consequences of genetic manipulation of alpha2. Taken together, these results lend further support to the concept of distinct isoform-specific functions of Na/K-ATPase alpha1 and alpha2 in skeletal muscle. |
