Abstract
The myosin regulatory light chain (R-LC) of type II fibers is phosphorylatable. Contraction-induced activation of a skeletal muscle specific Ca2+ - calmodulin-dependent myosin light chain kinase (MLCK) catalyzes the phosphorylation reaction, an event that may modulate myosin motor behavior. The influence of this molecular mechanism on the contractile performance of fatigued fast twitch skeletal muscle remains unclear, however. PURPOSE: To determine the effect of skeletal muscle MLCK gene ablation on the fatigability of force and velocity in mouse extensor digitorum longus (EDL) muscles. METHODS: Muscles from wildtype (WT) and skeletal MLCK knockout (KO) mice (n=10) were studied in vitro at 25° C during a fatigue protocol consisting of 5 minutes of repetitive high frequency stimulation (150 Hz for 1000 ms every 5 sec). Isometric twitch (Pt) and tetanic (Po) forces and unloaded shortening velocity (Vo) were assessed throughout the fatigue protocol. RESULTS: Pt was increased to a greater extent in WT than in KO muscles (36.8 ± 5.9% vs. 14.9 ± 2.7%, p < 0.05) during the initial stages of stimulation when Po was depressed less than 40% in both muscle types; thereafter, Pt declined to similar levels in both WT and KO muscles (to ∼ 35% of initial levels). On the other hand, values for Vo were greater for WT than for KO muscles (10.3 ± 0.90 vs. 8.4 ± 0.36 fiber lengths/s) during the final stages of stimulation, when Po was reduced ∼ 90% in both muscle types. CONCLUSION: These results suggest that MLCK gene ablation selectively impairs low frequency force during moderate fatigue and impairs unloaded shortening velocity during severe fatigue of fast twitch skeletal muscle. Supported by NSERC.
Published Version
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