Posttetanic potentiation improves neuromuscular efficiency of mouse muscle in vitro

Neuromuscular efficiency is defined as the ratio of work output to stimulation rate. The purpose of these experiments was to test the hypothesis that neuromuscular efficiency would be increased in proportion to posttetanic potentiation, that is, the stimulation-induced increase in work output displayed by rodent fast-twitch muscle. To this end, extensor digitorum longus muscles from wild-type and skeletal myosin light chain kinase knockout (skMLCK^-/- ) mice were surgically isolated and suspended in vitro (25°C). Concentric force development during shortening at 70% of maximal unloaded shortening velocity was tested at stimulus frequencies between 10 and 80 Hz both before and after a potentiating tetanus. A strong genotype-dependent difference in the potentiation of concentric work output was observed; concentric work output of wild-type muscles was increased by 51%-88% while that of skMLCK^-/- muscles was increased by only 20%-34% across the frequencies tested. As a result, comparison of work - frequency plots revealed that the frequency required for peak and 50% peak unpotentiated work of wild-type muscles was decreased from ~80 to 52 Hz and from ~48 to 21 Hz, respectively. By contrast, the frequency required for peak and 50% peak unpotentiated work of skMLCK^-/- muscles was decreased from ~80 to 68 Hz and from ~51 to 41 Hz, respectively. Thus, wild-type muscles with the ability to phosphorylate myosin displayed larger increases in neuromuscular efficiency than skMLCK^-/- muscles (25-30 vs 10-15 Hz, respectively). This suggests that the presence of myosin phosphorylation may ameliorate or mitigate fatigue mechanisms associated with high-frequency stimulation rates.