Regulatory light chain phosphorylation increases eccentric contraction–induced injury in skinned fast-twitch fibers

During contraction, activation of Ca²⁺/calmodulin–dependent myosin light chain kinase (MLCK) results in phosphorylation of myosin's regulatory light chain (RLC), which potentiates force and increases speed of force development over a wide range of [Ca²⁺]. We tested the hypothesis that RLC phosphorylation by MLCK mediates the extent of eccentric contraction–induced injury as measured by force deficit in skinned fast-twitch skeletal muscle fibers. Results indicated that RLC phosphorylation in single skinned rat psoas fibers significantly increased Ca²⁺ sensitivity of isometric force; isometric force from 50 ± 16 to 59 ± 18 kN/m² during maximal Ca²⁺ activation; peak absolute power output from 38 ± 15 to 48 ± 14 nW during maximal Ca²⁺ activation; and the magnitude of contraction-induced force deficit during maximal (pCa 4.5) activation from 26 ± 9.8 to 35 ± 9.6%. We conclude that RLC phosphorylation increases force deficits following eccentric contractions, perhaps by increasing the number of force-generating cross-bridges. Muscle Nerve 29: 313–317, 2004