Thick Filament Activation Is Different in Fast and Slow-Twitch Skeletal Muscle

Abstract

The contractile properties of fast-twitch and slow-twitch skeletal muscles are primarily determined by the myosin isoform content and modulated by a variety of sarcomere proteins. X-ray diffraction studies of regulatory mechanisms in muscle contraction have focused predominately on fast-or mixed-fiber muscle with slow muscle being much less studied. Here, we used time-resolved x-ray diffraction to investigate the dynamic behavior of the myofilament proteins in relatively pure slow fiber rat soleus (SOL) and pure fast fiber rat extensor digitorum longus (EDL) muscle during twitch and tetanic contractions at optimal length. During twitch contractions the diffraction signatures indicating a transition in the myosin heads from ordered OFF states, where heads are held close to the thick filament backbone, to disordered ON states, where heads are free to bind to thin filaments, were found in EDL and not in SOL muscle. During tetanic contraction, changes in the disposition of myosin heads as active tension develops is a cooperative process in EDL muscle whereas in SOL muscle this relationship is less cooperative. The observed reduced extensibility of the thick filaments in SOL muscle as compared to EDL muscles indicate a molecular basis for this behavior. These data indicate that for the EDL thick filament activation is a cooperative strain-induced mechano-sensing mechanism, whereas for the SOL thick filament activation has a more graded response. These different approaches to thick filament regulation in fast- and slow-twitch muscles may be adaptations for short duration, strong contractions versus sustained, finely controlled contractions, respectively. Key PointsO_LIFast twitch muscle and slow-twitch muscle are optimized for strong, short duration contractions and sustained smaller movements respectively. C_LIO_LIStructural events (OFF to ON transitions) in the myosin containing thick filaments in fast muscle help determine the timing and strength of contractions but these have not been studied in slow-twitch muscle. C_LIO_LIThe X-ray diffraction signatures of structural OFF to ON transitions are different in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle, being completely absent during twitches in soleus muscle and blunted during tetanic contractions SOL as compared to EDL C_LIO_LICooperative thick filament structural OFF to ON transitions in fast twitch muscle may be an adaptation for rapid and ballistic movements whereas more graded OFF to ON structural transitions in slow-twitch muscle may be an adaptation for slower, finer motions. C_LI