Myosin light chain phosphorylation and posttetanic potentiation in fatigued skeletal muscle

Myosin light chain (P-LC) phosphorylation, which is thought to be the principle mechanism for twitch potentiation in skeletal muscle, is significantly decreased during staircase in fatigued muscle. Attenuated phosphorylation of P-LC could be due to either depressed Ca2+ transients in fatigue, or to some inhibitory influence of contractile activity on myosin light chain kinase (MLCK). Tetanic stimulation, which would presumably result in maximal activation of MLCK, could be used to evaluate these potential mechanisms. P-LC phosphorylation and twitch developed tension (DT) were assessed at 20 and 120 s following a tetanic contraction in either rested or fatigued rat gastrocnemius muscle in situ. P-LC phosphorylation was significantly lower in fatigued muscles (39.7 +/- 3.2% vs 54.8 +/- 3. 5%, 20 s after a 2-s tetanic contraction), while posttetanic potentiation (PTP) was similar in fatigued (189.1 +/- 6.5%) versus rested muscle (169.5 +/- 2.6%). Tetanic DT was reduced following the fatigue protocol and, thus, the assumption that the MLCK system was fully activated by Ca2+ may not be valid. The potentiation-phosphorylation relationships were linear for both rested and fatigued muscles; however this relationship was shifted markedly leftward in fatigued muscles. It appears that during PTP, equivalent potentiation is attained with correspondingly lower levels of P-LC phosphorylation in fatigued muscle. This enhanced relative potentiation for a given level of phosphorylation could be expected if Ca2+ transients were attenuated in the fatigued muscle. However the results do not rule out the possibility that other factors contribute to potentiation under these circumstances.