دورية أكاديمية
Functional Characterization of the Intact Diaphragm in a Nebulin-Based Nemaline Myopathy (NM) Model-Effects of the Fast Skeletal Muscle Troponin Activator tirasemtiv
| العنوان: | Functional Characterization of the Intact Diaphragm in a Nebulin-Based Nemaline Myopathy (NM) Model-Effects of the Fast Skeletal Muscle Troponin Activator tirasemtiv |
|---|---|
| المؤلفون: | Eun-Jeong Lee, Justin Kolb, Darren T. Hwee, Fady I. Malik, Henk L. Granzier |
| المصدر: | International Journal of Molecular Sciences, Vol 20, Iss 20, p 5008 (2019) |
| بيانات النشر: | MDPI AG, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | muscle contraction, isometric force, shortening velocity, fast skeletal muscle troponin activators, diaphragm muscle, nebulin, nemaline myopathy, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Respiratory failure due to diaphragm dysfunction is considered a main cause of death in nemaline myopathy (NM) and we studied both isometric force and isotonic shortening of diaphragm muscle in a mouse model of nebulin-based NM (Neb cKO). A large contractile deficit was found in nebulin-deficient intact muscle that is frequency dependent, with the largest deficits at low−intermediate stimulation frequencies (e.g., a deficit of 72% at a stimulation frequency of 20 Hz). The effect of the fast skeletal muscle troponin activator (FSTA) tirasemtiv on force was examined. Tirasemtiv had a negligible effect at maximal stimulation frequencies, but greatly reduced the force deficit of the diaphragm at sub-maximal stimulation levels with an effect that was largest in Neb cKO diaphragm. As a result, the force deficit of Neb cKO diaphragm fell (from 72% to 29% at 20 Hz). Similar effects were found in in vivo experiments on the nerve-stimulated gastrocnemius muscle complex. Load-clamp experiments on diaphragm muscle showed that tirasemtiv increased the shortening velocity, and reduced the deficit in mechanical power by 33%. Thus, tirasemtiv significantly improves muscle function in a mouse model of nebulin-based nemaline myopathy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 |
| Relation: | https://www.mdpi.com/1422-0067/20/20/5008; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms20205008 |
| URL الوصول: | https://doaj.org/article/a93200207e6847c5a0dd5442d737ce60 |
| رقم الأكسشن: | edsdoj.93200207e6847c5a0dd5442d737ce60 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 |
|---|---|
| DOI: | 10.3390/ijms20205008 |