The effect of skeletal myosin light chain kinase gene ablation on the fatigability of XXXX fast muscle.

@entity141 @entity19 @entity56825 @entity23452
Contraction-induced activation of a skeletal muscle specific @entity141 and calmodulin dependent myosin light chain kinase (skMLCK) catalyzes phosphorylation of the @entity56825 , a reaction that potentiates twitch force. The purpose of this study was to test the effect of skMLCK gene ablation on the fatigability of @entity19 extensor digitorum longus (EDL) muscle (in vitro at 25  C). Muscles were isolated from wildtype (WT, n = 10-12) and skeletal @entity23452 knockout (skMLCK KO, n = 10-12) @entity19 and fatigued using a protocol consisting of 5 min of repeated tetanic stimulation (150 Hz for 1000 ms every 5 s). Both twitch (P(t)) and tetanic (P(o)) force as well as unloaded shortening velocity (V(o)) were assessed before, during and after fatiguing stimulation. Fatiguing stimulation increased @entity56825 phosphorylation in WT but not skMLCK KO muscles (16    0.01-0.63    0.02 and 0.07    0.02-0.08    0.02 mol phos mol @entity56825 , respectively). Although P(t) was potentiated above baseline in both WT and KO muscles, this increase was greater in WT than in KO muscles (to 1.37    0.05 vs. 1.14    0.02 of unpotentiated values, respectively). The difference in P(t) persisted until P(o) had been diminished to ~60% of baseline and thereafter P(t) declined to similar levels in both WT and KO muscles (to ~35% of initial). Overall, the time-course and decline in P(o) for WT and KO was similar (reduced to 0.20    0.01 and 0.20    0.01 of baseline, respectively) (P < 0.05). Initial values for V(o) were similar between WT and KO muscles and, moreover, the fatigue related decline in Vo was similar for both muscle genotypes (P < 0.05). Thus, our results demonstrate that skMLCK--catalyzed @entity56825 phosphorylation augments isometric twitch force during moderate, but not severe, levels of fatigue.
