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