What does chronic electrical stimulation teach us about muscle plasticity?

  title={What does chronic electrical stimulation teach us about muscle plasticity?},
  author={Dirk Pette and Gerta Vrb{\'o}va},
  journal={Muscle \& Nerve},
The model of chronic low‐frequency stimulation for the study of muscle plasticity was developed over 30 years ago. This protocol leads to a transformation of fast, fatigable muscles toward slower, fatigue‐resistant ones. It involves qualitative and quantitative changes of all elements of the muscle fiber studied so far. The multitude of stimulation‐induced changes makes it possible to establish the full adaptive potential of skeletal muscle. Both functional and structural alterations are caused… 

The Contribution of Neuromuscular Stimulation in Elucidating Muscle Plasticity Revisited

The chronic low-frequency stimulation experiment allows exploring many aspects of the plasticity of mammalian skeletal muscle and offers the possibility of elucidating molecular mechanisms that remodel phenotypic properties of a differentiated post-mitotic cell during adaptation to altered functional demands.

Application of animal models: chronic electrical stimulation-induced contractile activity.

The CLFS technique has great value for studying various aspects of muscle adaptation, and its wider scientific application to a variety of neuromuscular-based disorders in humans appears to be warranted.

Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise

  • K. Gundersen
  • Biology
    Biological reviews of the Cambridge Philosophical Society
  • 2011
It is suggested that changes in nerve‐evoked muscle activity lead to a variety of activity correlates such as increases in free intracellular Ca2+ levels caused by influx across the cell membrane and/or release from the sarcoplasmatic reticulum, concentrations of metabolites such as lipids and ADP, hypoxia and mechanical stress.

Molecular mechanisms of muscle plasticity with exercise.

A major current challenge is to verify and apply available knowledge gained in model systems to predict human phenotypic plasticity as well as understand the precise interactions among partners of signaling networks and accordingly models to predict signaling outcome of entire networks.

Calcium ion in skeletal muscle: its crucial role for muscle function, plasticity, and disease.

Functional alterations of Ca(2+) handling seem to be responsible for the pathophysiological conditions seen in dystrophinopathies, Brody's disease, and malignant hyperthermia, which underline the importance of the affected molecules for correct muscle performance.

Functional and biochemical properties of chronically stimulated human skeletal muscle

Investigation of the effects of chronic low-frequency stimulation of the knee extensor and hamstring muscles of both legs in healthy volunteers via surface electrodes found that an increase in aerobic-oxidative capacity was accompanied by improved work capacity and V̇O2 at the anaerobic threshold by 26% and 20%, respectively.

Chronic low-frequency stimulation upregulates uncoupling protein-3 in transforming rat fast-twitch skeletal muscle.

  • C. PutmanW. Dixon D. Pette
  • Biology
    American journal of physiology. Regulatory, integrative and comparative physiology
  • 2004
It is concluded that absolute increases in UCP-3 protein content in the early adaptive phase were associated with the genesis of mitochondria containing a normal complement of U CP-3, however, during exposure to long-term CLFS, mitochondria were generated with a lower complement and coincided with the emergence of a growing population of oxidative type IIA fibers.

Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen

Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units.

highlighted topics Plasticity in Skeletal, Cardiac, and Smooth Muscle Selected Contribution: Low-frequency stimulation of fast muscle affects the abundance of Ca 2 1 -ATPase but not its oligomeric status

Oligomerization appears to be of central importance to the proper physiological functioning of the Ca-ATPase and does not undergo changes during skeletal muscle conditioning, but changes in subunit interactions within Ca pump complexes contribute to this phenomena.

Adaptive change in electrically stimulated muscle: A framework for the design of clinical protocols

In this review, relevant factors, such as the amount, frequency, and duty cycle of stimulation, the influence of force generation, and the animal model are examined, and a framework emerges for the design of protocols that yield an overall functional profile appropriate to the application.



Altered gene expression in fast-twitch muscle induced by chronic low-frequency stimulation.

Increased neuromuscular activity via chronic low-frequency stimulation induces multiple fast-to-slow transitions in phenotypic properties that ultimately lead to fiber type conversions in the

Early functional and biochemical adaptations to low-frequency stimulation of rabbit fast-twitch muscle.

Altered in excitability, Ca2+ handling, and excitation-contraction coupling prior to changes in myofibrillar protein isoforms may be responsible for early functional alterations in rabbit tibialis anterior muscles.

Human skeletal muscle adaptation in response to chronic low-frequency electrical stimulation.

The results of the present study suggest that the muscle characteristics investigated in the current study have a limited capacity of adaptation in response to this form of chronic LFES.

Effects of chronic electrical stimulation on contractile properties of long‐term denervated rat skeletal muscle.

It is speculated that the final level of tension reached by unstimulated denervated muscles is an equilibrium between decrease in force due to atrophy and necrosis and increase due to regeneration, and differences between the final tension levels in soleus and EDL cannot be accounted for quantitatively by known differences in atrophy alone.

Effects of chronic low-frequency stimulation on Ca2+-regulatory membrane proteins in rabbit fast muscle

Findings support the physiological concept that there are muscle fiber-type specific differences in the fine-tuning of the excitation–contraction–relaxation cycle, as well as the idea that mature skeletal muscle fibers exhibit a high degree of plasticity.

Asynchronous increases in oxidative capacity and resistance to fatigue of electrostimulated muscles of rat and rabbit.

The dissociation between the changes of the two parameters studied suggests that factors other than elevated aerobic oxidative capacity contribute to enhanced resistance to fatigue.

Fast‐to‐slow transformation in stimulated rat muscle

Results taken together with the published analyses of myosin isoform composition of these muscles show that the mechanisms that control gene expression in response to activity are not exclusive to larger mammals.

Restoration of fast muscle characteristics following cessation of chronic stimulation: physiological, histochemical and metabolic changes during slow-to-fast transformation

The present experiments showed that stimulation-induced changes were completely reversible, and the muscles had recovered their original fast properties by about 12 weeks after the cessation of stimulation, which has important consequences for therapeutic applications that make use of the fatigue-resistant character of chronically stimulated muscle.

Transcriptional control of muscle plasticity: differential regulation of troponin I genes by electrical activity.

The results demonstrate that the linear arrangement of DNA sequence motifs is conserved in the regulatory elements of the TnI slow and fast genes and suggest that the interaction of multiple protein-DNA complexes are necessary for enhancer function.

Effect of chronic electrical stimulation on GLUT-4 protein content in fast-twitch muscle.

The results suggest that increased neuromuscular activity can act independently of systemic changes to increase total GLut-4 protein content and that both GLUT-4protein content and citrate synthase activity are positively related to increased neuromechanical activity but that their rates of increase differ substantially.