| First Author | Manoharan P | Year | 2015 |
| Journal | Am J Physiol Cell Physiol | Volume | 309 |
| Issue | 12 | Pages | C813-22 |
| PubMed ID | 26468207 | Mgi Jnum | J:233214 |
| Mgi Id | MGI:5780957 | Doi | 10.1152/ajpcell.00205.2015 |
| Citation | Manoharan P, et al. (2015) Phospholemman is not required for the acute stimulation of Na(+)-K(+)-ATPase alpha(2)-activity during skeletal muscle fatigue. Am J Physiol Cell Physiol 309(12):C813-22 |
| abstractText | The Na(+)-K(+)-ATPase alpha2-isoform in skeletal muscle is rapidly stimulated during muscle use and plays a critical role in fatigue resistance. The acute mechanisms that stimulate alpha2-activity are not completely known. This study examines whether phosphorylation of phospholemman (PLM/FXYD1), a regulatory subunit of Na(+)-K(+)-ATPase, plays a role in the acute stimulation of alpha2 in working muscles. Mice lacking PLM (PLM KO) have a normal content of the alpha2-subunit and show normal exercise capacity, in contrast to the greatly reduced exercise capacity of mice that lack alpha2 in the skeletal muscles. Nerve-evoked contractions in vivo did not induce a change in total PLM or PLM phosphorylated at Ser63 or Ser68, in either WT or PLM KO. Isolated muscles of PLM KO mice maintain contraction and resist fatigue as well as wild type (WT). Rb(+) transport by the alpha2-Na(+)-K(+)-ATPase is stimulated to the same extent in contracting WT and contracting PLM KO muscles. Phosphorylation of sarcolemmal membranes prepared from WT but not PLM KO skeletal muscles stimulates the activity of both alpha1 and alpha2 in a PLM-dependent manner. The stimulation occurs by an increase in Na(+) affinity without significant change in Vmax and is more effective for alpha1 than alpha2. These results demonstrate that phosphorylation of PLM is capable of stimulating the activity of both isozymes in skeletal muscle; however, contractile activity alone is not sufficient to induce PLM phosphorylation. Importantly, acute stimulation of alpha2, sufficient to support exercise and oppose fatigue, does not require PLM or its phosphorylation. |
