Overexpression of phospholamban in slow‐twitch skeletal muscle is associated with depressed contractile function and muscle remodeling
| Autor: | Karen B. Young, Evangelia G. Kranias, Michael J Gerst, James Gulick, Jeffrey Robbins, Qiujing Song, Guoxiang Chu, Ingrid L. Grupp |
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| Rok vydání: | 2004 |
| Předmět: |
Genetically modified mouse
endocrine system medicine.medical_specialty Contraction (grammar) Fluorescent Antibody Technique Mice Transgenic Stimulation Calcium-Transporting ATPases Biology Biochemistry Sarcoplasmic Reticulum Calcium-Transporting ATPases Mice Isometric Contraction Internal medicine Genetics medicine Animals Muscle Skeletal Molecular Biology Calcium metabolism Ryanodine receptor Calcium-Binding Proteins Isoproterenol Cardiac muscle Skeletal muscle musculoskeletal system Phospholamban Sarcoplasmic Reticulum Muscle Fibers Slow-Twitch Endocrinology medicine.anatomical_structure cardiovascular system Calcium Biotechnology |
| Zdroj: | The FASEB Journal. 18:974-976 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.03-1058fje |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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