Myosin phosphorylation‐mediated potentiation does not alter the economy of work performed in fast skeletal muscles

Abstract

The physiological role of myosin regulatory light chain (RLC) phosphorylation in fast skeletal muscle is unclear, as the resultant potentiation of contractile function comes with an undetermined energetic cost. We conducted in vitro experiments (25°C) to quantify contractile economy (i.e. energy cost/work performed) in potentiated extensor digitorum longus (EDL) muscles from wildtype and myosin light chain kinase knockout (skMLCK−/−) mice. Economy values were calculated as the ratio of total work performed to high‐energy phosphate consumption (HEPC) during a period of repeated isovelocity contractions that followed a potentiating stimulus (PS). The PS enhanced contractile parameters (concentric force and work) in both genotypes, although the effect was significantly greater in wildtype (1.38 ± 0.03 and 1.51 ± 0.03) vs. skMLCK−/− (1.10 ± 0.04 and 1.10 ± 0.05) muscles (P < 0.05, n = 8 for all data). During the experimental period of repetitive stimulation in the potentiated state, wildtype muscles performed ~58% more total work than skMLCK−/− muscles (94.05 ± 3.80 vs. 59.55 ± 4.10 J•kg−1; P < 0.001) without a statistical increase in HEPC (19.03 ± 3.37 vs. 16.02 ± 3.41 μmol~P; P = 0.27) or genotype difference in economy (5.74 ± 0.67 vs. 4.61 ± 0.71 J•kg−1μmol~P−1; P = 0.27). Importantly, when relative genotype differences were analyzed, the quantity of total work performed was ~3 fold greater than the increase in HEPC for wildtype muscles. Our results support the idea that myosin RLC phosphorylation‐mediated potentiation is a mechanism capable of augmenting sustained contractile function without significantly increasing energetic cost or decreasing economy.Support or Funding InformationNatural Sciences & Engineering Research Council of Canada (NSERC): Discovery Grant (R. Vandenboom)