| First Author | Song Q | Year | 2004 |
| Journal | FASEB J | Volume | 18 |
| Issue | 9 | Pages | 974-6 |
| PubMed ID | 15059971 | Mgi Jnum | J:127873 |
| Mgi Id | MGI:3765169 | Doi | 10.1096/fj.03-1058fje |
| Citation | Song Q, et al. (2004) Overexpression of phospholamban in slow-twitch skeletal muscle is associated with depressed contractile function and muscle remodeling. FASEB J 18(9):974-6 |
| abstractText | The relative amount of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and its crucial inhibitor phospholamban (PLN) are closely regulated and play a pivotal role in maintaining muscle function. The functional importance of PLN has been intensively investigated in cardiac muscle. However, little is known about the role of PLN in the slow-twitch skeletal muscle, which expresses a significantly lower level of PLN but a similar level of SERCA2a compared with cardiac muscle. Thus, to define the physiological significance of PLN in slow-twitch skeletal muscle, we generated transgenic mice with PLN-specific overexpression in soleus, which is largely composed of slow-muscle fibers. The PLN protein levels and the PLN/SERCA2a ratio in transgenic soleus were comparable with those in cardiac muscle. Assessment of isometric-twitch contractions indicated that PLN overexpression was associated with depressed rates of contraction and relaxation, which were not linked to reduced SERCA2a abundance, although the levels of other key Ca2+-handling proteins, including ryanodine receptor, FKBP12, and L-type Ca2+ channel, were significantly decreased. However, isoproterenol stimulation reversed the inhibitory effects of PLN on the transgenic soleus twitch kinetics. Furthermore, the PLN-overexpressing soleus had smaller muscle size, mass, and cross-sectional area compared with wild-types. Interestingly, the percentage of slow fibers was increased in PLN-overexpressing soleus. Taken together, these findings indicate that increased PLN expression in slow-twitch skeletal muscle is associated with impaired contractile function and muscle remodeling. |
