Excitation-contraction coupling and mechano-sensitivity in denervated skeletal muscles

Abstract

Skeletal muscle atrophy can be defined as a wasting or decrease in muscle mass and muscle force generation owing lack of use, ageing, injury or disease. Thus, the etiology of atrophy can be different. Atrophy in denervated muscle is a consequence of two factors: 1) the complete lack of motoneuron activity inducing the deficiency of neurotransmitter release and 2) the muscles disuse. The balance of the muscular functions depends on extra-and intra-muscular signals. In the balance are involved the excitation-contraction coupling (ECC), local growth factors, Ca 2+ -dependent and independent intracellular signals, mechano-sensitivity and mechano-transduction that activate Ca 2+ -dependent signaling proteins and cytoskeletonnucleus pathways to the nucleus, that regulate the gene expression. Moreover, retrograde signal from intracellular compartments and cytoskeleton to the sarcolemma are additional factors that regulate the muscle function. Proteolytic systems that operate in atrophic muscles progressively reduce the muscle protein content and so the sarcolemma, ECC and the force generation. In this review we will focus on the more relevant changes of the sarcolemma, excitation-contraction coupling, ECC and mechano-transduction evaluated by electrophysiological methods and observed from early-to long-term denervated skeletal muscles. This review put in particular evidence that long-term denervated muscle maintain a sub-population of fibers with ECC and contractile machinery able to be activated, albeit in lesser amounts, by electrical and mechanical stimulation. Accordingly, this provides a potential molecular explanation of the muscle recovery that occurs in response to rehabilitation strategy as transcutaneous electrical stimulation and passive stretching of denervated muscles, which wre developed as a result of empirical clinical observations. Key Words: Excitation-contraction coupling; L-type Ca 2+ current; Mechano-transduction; Skeletal muscle; Long-term denervation European Journal Translational Myology -Myology Reviews 2010; 1 (3): 121-130 Skeletal muscle atrophy can be defined as a wasting or decrease in muscle mass and muscle force generation owing lack of use, ageing, injury, or disease. Thus, the etiology of atrophy can be different. Atrophy resulting from disuse (muscle unloading, immobilization, bed rest, and spaceflight) and described as acute atrophy, is readily reversible by exercise and is the consequence of the lack of muscle activity that reduced the gene activation and protein synthesis. The age-related loss of muscle mass and strength, sarcopenia, may be considered to be chronic. Muscle atrophy resulting from chronic disease rather than disuse is described as cachexia and generally arises either from permanent damage of motoneurons or from muscle diseases. Both causes can be the result of either genetic abnormality of nerves or muscles, or systemic diseases. In motoneuron pathology muscle Excitation-contraction coupling in denervated muscleEuropean Journal Translational Myology -Myolo...

Cytoskeleton, L-type Ca2+ and stretch activated channels in injured skeletal muscle

“…This suggests a leaky sarcolemma and a reduced cytoskeleton expression/activity that, in turn, induces an increase of the intracellular Ca 2+ concentration, which was confirmed by the negative shift of the Ltype Ca 2+ current reversal potential. Moreover, the alteration of the cytoskeleton may not only increase the mechano-sensitivity of SACs but also that of L-type Ca 2+ channels [6]. The shift towards more positive potentials of L-type Ca 2+ current activation is directly involved in ECC and was formerly observed in the slow skeletal muscle fibres of the frog by using ryanodine or ruthenium red.…”

Facial muscle contraction in response to mechanical stretch after severe facial nerve injury: Clapham's sign

“…This suggests that the phenomenon reflects excitation–contraction coupling, and that the denervated cell membrane responds to stretch by depolarisation. There are known to be stretch-activated channels on the surface of muscle cells, which become more sensitive after denervation, although their role is unclear 10 …”