Extracellular magnesium and calcium reduce myotonia in isolated ClC‐1 chloride channel‐inhibited human muscle

  title={Extracellular magnesium and calcium reduce myotonia in isolated ClC‐1 chloride channel‐inhibited human muscle},
  author={Martin Skov and Frank Vincenzo Paoli and Jesper Lausten and Ole Baekgaard Nielsen and Thomas H. Pedersen},
  journal={Muscle \& Nerve},
Introduction: Experimental myotonia induced in rat muscle by ClC‐1 chloride channel‐inhibited has been shown to be related inversely to extracellular concentrations of Mg2+ and Ca2+ ([Mg2+]o and [Ca2+]o) within physiological ranges. Because this implicates a role for [Mg2+]o and [Ca2+]o in the variability of symptoms among myotonia congenita patients, we searched for similar effects of [Mg2+]o and [Ca2+]o on myotonia in human muscle. Methods: Bundles of muscle fibers were isolated from… 
Skeletal muscle ClC-1 chloride channels in health and diseases
The wide spectrum of pathophysiological conditions associated with modification of ClC-1 activity, either as the primary cause, such as in myotonia congenita, or as a secondary adaptive mechanism in other neuromuscular diseases, supports the idea that ClC -1 is relevant to preserve not only for skeletal muscle excitability, but also for skeletal Muscle adaptation to physiological or harmful events.
Depletion of ATP Limits Membrane Excitability of Skeletal Muscle by Increasing Both ClC1-Open Probability and Membrane Conductance
Results are compatible with ClC-1 function being regulated by the level of adenosine nucleotides in native tissue, and that the channel operates as a sensor of skeletal muscle metabolic state, limiting muscle excitability when energy status is low.
ClC-1 chloride channels: state-of-the-art research and future challenges
A recent de novo CLCN1 truncation mutation in a patient with generalized epilepsy indeed postulates an unexpected role of this channel in the control of neuronal network excitability.
Inhibiting persistent inward sodium currents prevents myotonia
The goal was to identify currents that trigger spontaneous firing of muscle in the setting of reduced ClC‐1 current.
Protein kinase C‐dependent regulation of ClC‐1 channels in active human muscle and its effect on fast and slow gating
The first demonstration of ClC‐1 inhibition in active human muscle fibres is presented, and the changes in ClC­1 gating that underlie the PKC‐dependent ClC-1 inhibition are determined using human ClC•1 expressed in Xenopus oocytes.
Lower Ca2+ enhances the K+-induced force depression in normal and HyperKPP mouse muscles
It is shown that lowering extracellular Ca2+ affects muscle contractility when the resting membrane potential is depolarized as in HyperKPP muscles and reduces the efficacy of salbutamol, a β2-adrenergic receptor agonist used to treatHyperKPP.
The mechanism underlying transient weakness in myotonia congenita
Transient weakness in myotonia congenita is caused by depolarization secondary to activation of persistent Na+ current in skeletal muscle, and targeting NaPIC with ranolazine prevents the development of plateau potentials and eliminates transient weakness in vivo.
Characterization of the TRPC3 Gene in Myotonic Goats: Further Insight Into Myotonia congenita and Muscular Dystrophy
The data indicate that the TRPC3 gene is a potential biomarker to further study Myotonia congenita in Myotonic goats and the interrelationship of the mechanism of calcium signaling in human Mc and MD.
The anti‐convulsants lacosamide, lamotrigine, and rufinamide reduce myotonia in isolated human and rat skeletal muscle
This study explored whether 3 sodium channel‐modulating anti‐epileptics can reduce myotonia in isolated rat and human muscle.


Extracellular magnesium and calcium reduce myotonia in ClC-1 inhibited rat muscle
Regulation of ClC-1 and KATP channels in action potential–firing fast-twitch muscle fibers
GCl and GK are acutely regulated in AP-firing fast-twitch muscle fibers and may contribute to the physiological control of excitability in active muscle.
Kinetic and pharmacological properties of the sodium channel of frog skeletal muscle
Na channels of frog skeletal muscle are studied under voltage clamp and their properties compared with those of frog myelinated nerve and it is concluded that Na channels of nerve and muscle are nearly the same.
Comparison of regulated passive membrane conductance in action potential–firing fast- and slow-twitch muscle
It is concluded that regulation of Gm is a general phenomenon in AP-firing muscle, and that differences in Gm regulation may contribute to the different phenotypes of fast- and slow-twitch muscle.
Measurement of Free Magnesium in Blood, Serum and Plasma with an Ion-Sensitive Electrode
The circadian rhythm of iMg2+ was found to be considerably more pronounced than that of total Mg and was negatively correlated to changes of free fatty acids and the accuracy of "Microlyte Magnesium" (Kone Instruments, Finland) is sufficient in a wide range of i Mg2+.
Myotonia congenita.
Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH.
Evidence is given for a high density of negative surface charge near the sodium channel of myelinated nerve fibres. The voltage dependence of peak sodium permeability is measured in a voltage clamp.
Magnesium in Disease: a Review with Special Emphasis on the Serum Ionized Magnesium
Most of the clinical situations studied show hypomagnesemia due to renal loss, with exception of renal disease, and measuring ionized magnesium in serum has little added value at present.
Phenotypic variability in myotonia congenita
The phenotype depends on the mutation type to some extent, but this does not explain the fact that severity varies greatly between heterozygous family members and may even vary with time in the individual patient.
Differential diagnosis of myotonic disorders
  • T. Miller
  • Medicine, Psychology
    Muscle & nerve
  • 2008
The presence of myotonia and paramyotonia on clinical examination and of myotonic discharges during electrodiagnostic (EDX) studies are important for the diagnosis of certain neuromuscular