INCREASED FORCE DEVELOPMENT RATES OF FATIGUED MOUSE SKELETAL-MUSCLE ARE GRADED TO MYOSIN LIGHT-CHAIN PHOSPHATE CONTENT

Phosphorylation of myosin regulatory light chain (R-LC) increases the Ca2+ sensitivity of cross-bridge transitions, which determine rate of force development in skinned skeletal muscle fibers. The purpose of th is study was to determine whether phosphorylation of R-LC is the molec ular basis for the increased force development rates (+dF/dt(max) obse rved in fatigued mouse extensor digitorum longus muscle (EDL) (stimula ted in vitro at 25 degrees C). Parameters of twitch and tetanic force were obtained after the application of different-frequency conditionin g stimuli (CS), which were used to vary R-LC phosphorylation and reduc e peak tetanic force (P-o). Without CS, R-LC phosphorylation tin moles phosphate per mole R-LC) was not elevated above rest (0.11 +/- 0.02 v s. 0.13 +/- 0.02, respectively), and no aspect of the twitch (P-t) P-o was altered. Stimulating muscles at 2.5-20 Hz increased R-LC phosphor ylation in a frequency-dependent manner, from 0.23 +/- 0.04 to 0.82 +/ - 0.03, respectively. Moreover, stimulation at 2.5-20 Hz potentiated P -t (range: 4 +/- 2-28 +/- 2%), increased the +dF/dt(max) of potentiate d twitches (range: 5 +/- 1-28 +/- 2%), and reduced P-o (range: 6 +/- 1 -21 +/- 1%). Higher-frequency stimulation (40 or 100 Hz) did not phosp horylate R-LC or potentiate P-t or twitch +dF/dt(max) further. Stimula tion at 40 and 100 Hz did, however, have different effects on P-o comp ared with 20-Hz data (P-o reduced 27 +/- 2 and 11 +/- 2%, respectively ). The increased +dF/dt(max) of potentiated twitches observed after di fferent CS procedures were graded to R-LC phosphorylation (r = 0.97, P < 0.001). It is concluded that phosphorylation of R-LC increases exte nt of twitch force development in mouse EDL muscle fatigued by CS.