Impaired Intracellular Ca2+ Dynamics, M-Band and Sarcomere Fragility in Skeletal Muscles of Obscurin KO Mice
Autor: | Enrico Pierantozzi, Péter Szentesi, Cecilia Paolini, Beatrix Dienes, János Fodor, Tamás Oláh, Barbara Colombini, Dilson E. Rassier, Egidio Maria Rubino, Stephan Lange, Daniela Rossi, László Csernoch, Maria Angela Bagni, Carlo Reggiani, Vincenzo Sorrentino |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Male
Muscle Fibers Skeletal/metabolism Kinetics of contraction Ankyrins/metabolism Calcium/metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism QH301-705.5 Sarcoplasmic reticulum Calcium dynamics Exercise Muscle fiber damage Obscurin Skeletal muscle Catalysis Inorganic Chemistry Mice Sarcoplasmic Reticulum/metabolism Physical Conditioning Animal obscurin skeletal muscle calcium dynamics muscle fiber damage kinetics of contraction sarcoplasmic reticulum exercise Sarcomeres/metabolism Animals Biology (General) Physical and Theoretical Chemistry Rho Guanine Nucleotide Exchange Factors/genetics QD1-999 Molecular Biology Muscle Proteins/metabolism Spectroscopy Connectin/metabolism Mice Knockout Muscle Skeletal/metabolism Organic Chemistry General Medicine musculoskeletal system Computer Science Applications Chemistry Protein Serine-Threonine Kinases/genetics Muscle Contraction/physiology |
Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1319 International Journal of Molecular Sciences, Vol 23, Iss 1319, p 1319 (2022) Pierantozzi, E, Szentesi, P, Paolini, C, Dienes, B, Fodor, J, Oláh, T, Colombini, B, Rassier, D E, Rubino, E M, Lange, S, Rossi, D, Csernoch, L, Bagni, M A, Reggiani, C & Sorrentino, V 2022, ' Impaired Intracellular Ca 2+ Dynamics, M-Band and Sarcomere Fragility in Skeletal Muscles of Obscurin KO Mice. ', International Journal of Molecular Sciences, vol. 23, no. 3 . https://doi.org/10.3390/ijms23031319 |
DOI: | 10.3390/ijms23031319 |
Popis: | Obscurin is a giant sarcomeric protein expressed in striated muscles known to establish several interactions with other proteins of the sarcomere, but also with proteins of the sarcoplasmic reticulum and costameres. Here, we report experiments aiming to better understand the contribution of obscurin to skeletal muscle fibers, starting with a detailed characterization of the diaphragm muscle function, which we previously reported to be the most affected muscle in obscurin (Obscn) KO mice. Twitch and tetanus tension were not significantly different in the diaphragm of WT and Obscn KO mice, while the time to peak (TTP) and half relaxation time (HRT) were prolonged. Differences in force-frequency and force-velocity relationships and an enhanced fatigability are observed in an Obscn KO diaphragm with respect to WT controls. Voltage clamp experiments show that a sarcoplasmic reticulum’s Ca2+ release and SERCA reuptake rates were decreased in muscle fibers from Obscn KO mice, suggesting that an impairment in intracellular Ca2+ dynamics could explain the observed differences in the TTP and HRT in the diaphragm. In partial contrast with previous observations, Obscn KO mice show a normal exercise tolerance, but fiber damage, the altered sarcomere ultrastructure and M-band disarray are still observed after intense exercise. |
Databáze: | OpenAIRE |
Externí odkaz: |