The excitation-contraction-relaxation cycle (E-C-R) in the mammalian twitch muscle comprises the following major events: (1) initiation and propagation of an action potential along the sarcolemma and transverse (T)-tubular system; (2) detection of the T-system depolarization signal and signal transmission from the T-tubule to the sarcoplasmic reticulum (SR) membrane; (3) Ca2+ release from the SR; (4) transient rise of myoplasmic [Ca2+]; (5) transient activation of the Ca2+-regulatory system and of the contractile apparatus; (6) Ca2+ reuptake by the SR Ca2+ pump and Ca2+ binding to myoplasmic sites. There are many steps in the E-C-R cycle which can be seen as potential sites for muscle fatigue and this review explores how structural and functional differences between the fast- and slow-twitch fibres with respect to the E-C-R cycle events can explain to a great extent differences in their fatiguability profiles.

There are consistent observations that depletion of intracellular glycogen stores in muscle is associated with reduced muscle performance (Bergstr om et al. 1967;Galbo et al. 1979;Voellestad et al. 1988;Fitts, 1994;Chin & Allen, 1997), but the cellular mechanisms responsible for the glycogen depletion-related impairment of muscle function are not understood (Fitts 1994;Chin & Allen, 1997). So far, all studies on the role of glycogen in muscle have involved the depletion of the muscle glycogen pool by inducing a state of muscle fatigue. Therefore, from these studies it is not possible to draw unequivocal conclusions concerning the nature of the relationship between glycogen content and muscle contractility because in addition to glycogen depletion, many other factors, known to affect excitation-contraction (E-C) coupling (Stephenson et al. 1998), would have been altered in the myoplasm of the fatigued muscle fibres. Further advances can be made if the relationship between glycogen and muscle contractility is investigated in single fibres containing different concentrations of glycogen under conditions where the ionic composition of the myoplasmic environment is kept constant and similar to that in a rested muscle. The mechanically skinned single muscle fibre preparation is particularly well suited for such a task

Chemically skinned single fibers from adult rat skeletal muscles were used to test the hypothesis that, in mammalian muscle fibers, myosin heavy chain (MHC) isoform expression and Ca(2+)- or Sr(2+)-activation characteristics are only partly correlated. The fibers were first activated in Ca(2+)- or Sr(2+)-buffered solutions under near-physiological conditions, and then their MHC isoform composition was determined electrophoretically. Fibers expressing only the MHC I isoform could be appropriately identified on the basis of either the Ca(2+)- or Sr(2+)-activation characteristics or the MHC isoform composition. Fibers expressing one or a combination of fast MHC isoforms displayed no significant differences in their Ca(2+)- or Sr(2+)-activation properties; therefore, their MHC isoform composition could not be predicted from their Ca(2+)- or Sr(2+)-activation characteristics. A large proportion of fibers expressing both fast- and slow-twitch MHC isoforms displayed Ca(2+)- or Sr(2+)-activation properties that were not consistent with their MHC isoform composition; thus both fiber-typing methods were needed to fully characterize such fibers. These data show that, in rat skeletal muscles, the extent of correlation between MHC isoform expression and Ca(2+)- or Sr(2+)-activation characteristics is fiber-type dependent.

son. Denervation produces different single fiber phenotypes in fast-and slow-twitch hindlimb muscles of the rat. Am J Physiol Cell Physiol 291: C518 -C528, 2006. First published April 12, 2006 doi:10.1152/ajpcell.00013.2006.-Using a single, mechanically skinned fiber approach, we tested the hypothesis that denervation (0 to 50 days) of skeletal muscles that do not overlap in fiber type composition [extensor digitorum longus (EDL) and soleus (SOL) muscles of Long-Evans hooded rats] leads to development of different fiber phenotypes. Denervation (50 day) was accompanied by 1) a marked increase in the proportion of hybrid IIB/D fibers (EDL) and I/IIA fibers (SOL) from 30% to Ͼ75% in both muscles, and a corresponding decrease in the proportion of pure fibers expressing only one myosin heavy chain (MHC) isoform; 2) complex muscle-and fiber-type specific changes in sarcoplasmic reticulum Ca 2ϩ -loading level at physiological pCa ϳ7.1, with EDL fibers displaying more consistent changes than SOL fibers; 3) decrease by ϳ50% in specific force of all fiber types; 4) decrease in sensitivity to Ca 2ϩ , particularly for SOL fibers (by ϳ40%); 5) decrease in the maximum steepness of the force-pCa curves, particularly for the hybrid I/IIA SOL fibers (by ϳ35%); and 6) increased occurrence of biphasic behavior with respect to Sr 2ϩ activation in SOL fibers, indicating the presence of both slow and fast troponin C isoforms. No fiber types common to the two muscles were detected at any time points (day 7, 21, and 50) after denervation. The results provide strong evidence that not only neural factors, but also the intrinsic properties of a muscle fiber, influence the structural and functional properties of a particular muscle cell and explain important functional changes induced by denervation at both whole muscle and single cell levels. mechanically skinned fibers; myosin heavy chain isoforms; lineage; sarcoplasmic reticulum; Ca 2ϩ and Sr 2ϩ sensitivity; Long-Evans hooded rat MAMMALIAN SKELETAL MUSCLE fibers display a broad spectrum of structural and functional characteristics determined by the complement of homologous, but not identical, molecular structures involved in the excitation-contraction-relaxation cycle (33,34,41). Cross-innervation (4, 6), denervation (16,17,26,28,37), and chronic low-frequency stimulation (7,20,33,34) experiments have produced compelling evidence that the pattern of neural stimulation plays a crucial role in determining the functional and/or structural properties of skeletal muscle (38). However, neural control of fiber phenotype does not extend to the entire complement of cellular structures responsible for muscle fiber function, as demonstrated by crossinnervation studies. For example, when the extensor digitorum longus (EDL) muscle of the rat, a typically fast-twitch muscle, was cross-innervated by the nerve of the soleus (SOL) muscle, a typically slow-twitch muscle, the twitch time course of the cross-innervated muscle remained considerably faster than the twitch of the typical SOL muscle, even 16 ...