HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/4/C881    most recent 00063.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Han, R. Articles by Bakker, A. J. Search for Related Content PubMed PubMed Citation Articles by Han, R. Articles by Bakker, A. J.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Effect of indomethacin on force responses and sarcoplasmic reticulum function in skinned skeletal muscle fibers and cytosolic [Ca²⁺] in myotubes

¹School of Biomedical and Chemical Sciences, and ²School of Anatomy and Human Biology, The University of Western Australia, Crawley, Western Australia 6009, Australia

Submitted 19 February 2003 ; accepted in final form 13 June 2003

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 fibers of the rat. The nonspecific PLA₂ inhibitor indomethacin (200 µM) significantly increased the peak (2-fold, P = 0.02) and the width (6-fold, P = 0.008) of depolarization-induced force responses (DIFRs) elicited in the fibers (n = 4). Exposure of the skinned EDL fibers 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 rundown. However, aristolochic acid (100 µM), an inhibitor of secretory PLA₂, failed to return DIFRs after rundown. Indomethacin did not protect against the loss of DIFRs induced by exposure to elevated myofibrilar [Ca²⁺]. Indomethacin (200 µM) produced a small but significant increase in the Ca²⁺ sensitivity of the contractile apparatus of skinned EDL fibers and the maximum force production. Indomethacin (200 µM) also had significant effects on SR function, increasing SR Ca²⁺ loading in the skinned fibers (117.2 ± 3.0% of controls, P = 0.0008, n = 8) and inducing intracellular Ca²⁺ release in isolated intact flexor digitorum brevis (FDB) fibers (n = 7) and C₂C₁₂ myotubes (n = 6). These data suggest that intracellular PLA₂ may be an important modulator of ECC in skeletal muscle.

phospholipase A₂; excitation-contraction coupling