Submitted on February 19, 2003
Accepted on June 13, 2003
Effect of Indomethacin on Force Responses and Sarcoplasmic Reticulum Function in Skinned Skeletal Muscle Fibres and Cytosolic [Ca2+] in Myotubes
Renzhi Han1*, Takuya Suizu1, Miranda D Grounds2, and Anthony J Bakker1
1 Physiology, The University of Western Australia, Perth, WA, Australia
2 Anatomy and Human Biology, The University of Western Australia, Perth, WA, Australia
* To whom correspondence should be addressed. E-mail: hanr{at}graduate.uwa.edu.au.
In this study, the effects of phospholipase A2 (PLA2) inhibitors on excitation-contraction coupling (ECC) and sarcoplasmic reticulum (SR) function were examined in skinned extensor digitorum longus (EDL) muscle fibres of the rat. The non-specific PLA2 inhibitor indomethacin (200 µM) significantly increased the peak (~2 fold, p=0.02) and the width (~6 fold, p=0.008) of the depolarisation-induced force responses (DIFRs) elicited in the fibres (n=4). Exposure of the skinned EDL fibres to indomethacin (200 µM) (n=7) and another PLA2 inhibitor quinacrine (200 µM) (n=5) resulted in the return of large DIFRs after use-dependent run-down. However, aristolochic acid (100 µM), an inhibitor of secretory PLA2, failed to return DIFRs after run-down. Indomethacin did not protect against loss of DIFRs induced by exposure to elevated intracellular [Ca2+]. Indomethacin (200 µM) produced a small but significant increase in the Ca2+ sensitivity of the contractile apparatus of skinned EDL fibres and the maximum force production. Indomethacin (200 µM) also had significant effects on SR function, increasing SR Ca2+ loading in the skinned fibres (117.2 ± 3.0 % of controls, p=0.0008, n=8) and inducing intracellular Ca2+ release in isolated intact flexor digitorum brevis (FDB) fibres (n=7) and C2C12 myotubes (n=6). These data suggest that intracellular PLA2 may be an important modulator of ECC in skeletal muscle.
