Na+‐K+‐ATPase is not involved in the warming‐up phenomenon in generalized myotonia

  title={Na+‐K+‐ATPase is not involved in the warming‐up phenomenon in generalized myotonia},
  author={Mireille C. P. van Beekvelt and Gea Drost and Gerard A Rongen and Dick F. Stegeman and Baziel G. M. van Engelen and Machiel Zwarts},
  journal={Muscle \& Nerve},
The initial temporary weakness that occurs in autosomal‐recessive generalized myotonia diminishes with repetitive contractions. Physiological understanding of this phenomenon is incomplete. The underlying hypothesis of our study was that the “warming‐up” phenomenon relates to the exercise‐related activation of Na+‐K+‐ATPase. Three patients performed isometric exercise of the brachioradialis muscle on two separate days. Randomly, on one of these days the contraction was preceded by a 30‐min… 
Preclinical pharmacological in vitro investigations on low chloride conductance myotonia: effects of potassium regulation
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In a drug-induced model of mechanical myotonia, fatigue-inducing stimulation resolves the myotonic effects, which furthermore appears to be independent from the development of muscle fatigue.
Channelopathies of skeletal muscle excitability.
A synthesis of the mechanistic connections between functional defects of mutant ion channels, their impact on muscle excitability, how these changes cause clinical phenotypes, and approaches toward therapeutics is provided.
Skeletal muscle fatigue: cellular mechanisms.
Most of the mechanistic studies of fatigue are on isolated animal tissues, and another major challenge is to use the knowledge generated in these studies to identify the mechanisms of fatigue in intact animals and particularly in human diseases.
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QMA is an automated, non‐invasive technique for evaluating myotonia in NDM and sodium channel mutations were associated with prolonged first handgrip relaxation times and paradoxicalMyotonia or warm‐up, depending on underlying mutations.
Sodium channel slow inactivation as a therapeutic target for myotonia congenita
The goal was to identify the mechanism underlying warmup and to use this information to guide development of novel therapy in patients with myotonia congenita.
Physiology and Pathophysiology of CLC-1: Mechanisms of a Chloride Channel Disease, Myotonia
The inheritance pattern of some but not all myotonia mutants can be explained by a working hypothesis that these mutations may exert a “dominant negative” effect on the gating function of the channel, which will require the understanding of multiple molecular/cellular mechanisms of CLC-1 channels in skeletal muscles.
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The phenotypical characteristics of NDM in both ClCh and NaCh are redefined to help clinicians working in outpatient clinics to perform a focused genetic analysis of either CLCN1 or SCN4A.
Myotonia congenita.
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It is concluded that sEMG may be useful to detect the presence of neuromuscular disease (level C rating, class III data), but there are insufficient data to support its utility for distinguishing between neuropathic and myopathic conditions or for the diagnosis of specific neuromoscular diseases.


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Ischaemic preconditioning is not involved in changes in MFCV during repeated ischaemic isometric exercise and the increase in M FCV to supranormal levels during recovery from ischaemia exercise is caused by rapid activation of Na+−K+‐ATPase.
Influence of extracellular potassium and intracellular pH on myotonia
It is concluded that although changes of extracellular K+ influence both myotonia and the warmup, these changes are unlikely to explain warmup in myotonic patients.
Regulation of Na+–K+ pump activity in contracting rat muscle
The results indicate that excitation rapidly activates the Na+–K+ pump, partly via a change in its transport characteristics and partly via an increase in intracellular Na+ concentration, which allows an approximately 20‐fold increase in the rate of Na+ efflux to take place within 10 s.
Rippling muscle disease may be caused by “silent” action potentials in the tubular system of skeletal muscle fibers
Recent data are discussed showing that action potentials can travel over substantial distances entirely within the transverse and longitudinal tubular systems of a muscle fiber and that stretch can induce suchaction potentials.
Maintaining Constant Voluntary Force in Generalized Myotonia Despite Muscle Membrane Disturbances: Insights from a High-Density Surface EMG Study
Using high-density surface EMG (SEMG), the authors tested the hypothesis that in patients with GM, muscle membrane function is already disturbed at low force levels despite constant force and that abnormal motor unit recruitment acts as a compensatory mechanism to obtain normal force stability.
Propagation disturbance of motor unit action potentials during transient paresis in generalized myotonia: a high-density surface EMG study.
It is concluded that the transient paresis is explained by a deteriorating muscle membrane function, ending in conduction block and pareis, and shows how spatiotemporal information, available through non-invasive high-density sEMG, may provide novel insights into electrophysiological aspects of membrane dysfunction.
Effect of transverse‐tubular chloride conductance on excitability in skinned skeletal muscle fibres of rat and toad
It is unequivocally demonstrate that there is a large 9‐AC‐sensitive Cl− conductance in the T‐ system of rat fibres, and a smaller, though still appreciable, Cl− Conductance inThe T‐system of toad fibres , which is relatively insensitive to 9‐ AC.
Downregulation of Na+-K+-ATPase pumps in skeletal muscle with training in normobaric hypoxia.
The results demonstrate that normobaric hypoxia induced during exercise training represents a potent stimulus for the upregulation in mitochondrial potential while at the same time promoting a downregulation in Na+-K+-ATPase pump expression.
Na+-K+ pump regulation and skeletal muscle contractility.
  • T. Clausen
  • Biology, Medicine
    Physiological reviews
  • 2003
The Na+-K+ pump is a central target for regulation of Na-k+ distribution and excitability, essential for second-to-second ongoing maintenance of excitability during work.
Changes of action potentials and force at lowered [Na+]o in mouse skeletal muscle: implications for fatigue.
The reduced contractility in nonfatigued muscles at lowered [Na+]o was largely due to 1) an increased number of inexcitable fibers and threshold for action potentials, 2) a reduction of action potential amplitude, and 3) a reduced capacity to generateaction potentials throughout trains.