The electrical properties of muscle fiber membranes in dystrophia myotonica and myotonia congenita.

McComas, Alan J.; Mrozek, K

doi:10.1136/jnnp.31.5.441

Cited by 43 publications

(19 citation statements)

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“…Electromyographically, myotonia is characterized by repetitive bursts of activity, which increase and decrease in frequency (2). Myotonia is seen not only in MyD but also in other syndromes such as human myotonia congenita (3,4), which resembles myotonia in goats and appears to be related to a decrease in muscle membrane chloride conductance (5,6). However, a decreased chloride conductance has not been demonstrated in MyD and the cause of myotonia in MyD remains undetermined.…”

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confidence: 99%

“…In biopsied MyD muscle fibers, these membrane abnormalities are expressed as a decreased resting membrane potential (4,(10)(11)(12) and an increased tendency to fire repetitive action potentials (11). The presence of denervation, degeneration, fat and connective tissue infiltration, and the decreased viability ofbiopsied tissue limit the possible electrophysiological analyses.…”

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confidence: 99%

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Cultured muscle from myotonic muscular dystrophy patients: altered membrane electrical properties.

Merickel¹,

Gray²,

Chauvin³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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Myotonic muscular dystrophy (MyD) is an inherited human disease involving skeletal muscle as well as many other organ systems. We have approached the study of this disorder by growing normal and diseased human muscle in a primary tissue culture system and investigating some of the electrical properties of the resulting myotubes. The most distinctive abnormality noted in MyD myotubes was an increased tendency to fire repetitive action potentials. A decreased action potential afterhyperpolarization amplitude and the presence of depolarizing afterpotentials were also noted, as were a decreased resting membrane potential, decreased action potential amplitude and overshoot, and decreased outward-going rectification. Although the ionic basis of these abnormal properties in vitro is not clearly defined, changes in the slow outward-going potassium current offer the best explanation. Furthermore, MyD cell culture offers a valuable mode for critical analysis of the molecular mechanisms underlying MyD deficits.Myotonic muscular dystrophy (MyD) is an inherited human disease with muscle wasting, weakness, and stiffness as prominent clinical manifestations. Other systems may also be involved, and patients may experience cardiovascular, ophthalmologic, endocrine, and gastrointestinal problems. The primary metabolic defect in MyD is not known.One of the clinical hallmarks of this disorder is myotonia, which is manifested as stiffness and difficulty in relaxing a muscle after voluntary contraction (1). Electromyographically, myotonia is characterized by repetitive bursts of activity, which increase and decrease in frequency (2). Myotonia is seen not only in MyD but also in other syndromes such as human myotonia congenita (3, 4), which resembles myotonia in goats and appears to be related to a decrease in muscle membrane chloride conductance (5, 6). However, a decreased chloride conductance has not been demonstrated in MyD and the cause of myotonia in MyD remains undetermined.Recent studies of erythrocytes (7,8) and muscle (9) from patients with MyD suggest abnormalities in the surface membranes of different tissues. In biopsied MyD muscle fibers, these membrane abnormalities are expressed as a decreased resting membrane potential (4, 10-12) and an increased tendency to fire repetitive action potentials (11). The presence of denervation, degeneration, fat and connective tissue infiltration, and the decreased viability ofbiopsied tissue limit the possible electrophysiological analyses.We

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Cultured muscle from myotonic muscular dystrophy patients: altered membrane electrical properties.

Merickel¹,

Gray²,

Chauvin³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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“…Measurement of the cable parameters was one of our primary goals. Based upon our experience with muscle from goats with hereditary myotonia (1,2), that of Norris (35), and McComas and Mrozek (36) in human myotonia congenita, a means of avoiding the repetitive electrical activity associated with microelectrode penetration was necessary in order to make the cable measurements. Tetrodotoxin was selected for this purpose because of its selective blockade of the sodium mechanism involved in the action potential (37,38).…”

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confidence: 99%

Cable parameters, sodium, potassium, chloride, and water content, and potassium efflux in isolated external intercostal muscle of normal volunteers and patients with myotonia congenita

Lipicky¹,

Bryant²,

Salmon³

1971

J. Clin. Invest.

149

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A B S T R A C T In isolated fiber bundles of external intercostal muscle from each of 13 normal volunteers and each of 6 patients with myotonia congenita, some or all of the following were measured: concentrations of Na+, K+, and Cl-, extracellular volume, water content, K+ efflux, fiber size, fiber cable parameters, and fiber resting potentials.Muscle from patients with myotonia congenita differed significantly (0.001 < P< 0.025) with respect to the following mean values (myotonia congenita vs. normal): the membrane resistance was greater (5729 vs. 2619 U. cm2), the internal resistivity was less (75.0 vs. 123.2 Q-cm), the water content was less (788.2 vs. 808.2 ml/kg wet weight), and the mean resting potential was greater (68 vs. 61 mv).No significant differences were found with respect to the following variables: K+ content (73.5 vs. 66.7 mEq/kg wet weight) and the calculated intracellular K+ concentration (215 vs. 191 mEq/liter fiber water), fiber capacitance (5.90 vs. 5.15 Mf/cm2), Na+ content (97.7 vs. 94.1 mEq/kg wet weight), 74.7 mEq/kg wet weight), mannitol extracellular volume (45.1 vs. 46.6 cc/100 g wet weight), and K+ efflux (23.2 vs. 21.5 moles X 10-12 cm-2.sec-1).These abnormalities of skeletal muscle in human myotonia congenita are like those of skeletal muscle in goats with hereditary myotonia. We tentatively conclude that a decreased Cl-permeability accounts for some of the abnormal electrical properties of skeletal muscle in myotonia congenita. We now report findings in isolated external intercostal muscle from patients with myotonia congenita and from normal volunteers. We have compared our human results with similar data we obtained in isolated external intercostal muscle from the goat (1, 2). METHODS Normal volunteers. Our normals are 13 males aged 21-33 yr with no evidence of neuropathy or myopathy. One (R. G.) had diabetes mellitus; another (T. P.) had probable pulmonary sarcoidosis (minimal pulmonary fibrosis on chest X-ray and scalene node biopsy positive for noncaseating granuloma). At the time of muscle biopsy, T. P. had no symptoms and his chest X-ray was clearer (without therapy) than 1 yr earlier. No volunteer had taken any medication for at least 5 days before the external intercostal muscle biopsy except for the patient with diabetes, who received insulin up to and including the day before biopsy. The remaining 11 subjects were healthy and the results of laboratory studies (chest X-ray, electrocardiogram, hemoglobin, hematocrit, white blood cell count and differential, urinalysis, serum urea nitrogen, fasting blood sugar, Wasserman, serum creatinine, serum ions [Na+, K+, Cl-], serum Ca and Mg, total serum proteins, serum alkaline phosphatase, serum glutamic oxalacetic transaminase, and creatinine phosphokinase) were normal. Biopsy techniques. Biopsies of the anterior border of external intercostal muscle (2.5-5 cm in length) were obtained under local anesthesia from the right eighth intercostal space. Preoperative medications were pentobarbital (from 100 to 200 mg), and morphin...

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“…Other studies performed with hereditary myotonic goats have led to the suggestion by extrapolation that human myotonia congenita results from a reduction of membrane permeability to chloride. In myotonia congenita, the resting membrane potential is not changed and a normal size depolarization is still required to initiate action potentials (28). However, a small variation of Na+ conductance could in that case exert a stronger than normal depolarizing action since it could only be balanced by potassium channels and not, as in normal membranes, by the combined effects of potassium and chloride channels.…”

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“…This disease is known to be a systemic genetic disorder inherited as an autosomal dominant trait. Electrophysiological studies have shown that the resting membrane potential is reduced (28,(30)(31)(32)(33) and that the membrane resistance is slightly increased (34). The overshoot of the action potential is not significantly affected (32) or only slightly decreased (33) and, like in normal muscle, the action potential is completely abolished after a 3-min exposure to 1 ,M TTX (7,33).…”

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Sodium Channel and Sodium Pump in Normal and Pathological Muscles from Patients with Myotonic Muscular Dystrophy and Lower Motor Neuron Impairment

Desnuelle¹,

Lombet²,

Serratrice³

et al. 1982

J. Clin. Invest.

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A B S T R A C T Two sodium transport systems have been analyzed in this work: the voltage-sensitive sodium channel and the (Na+, K+) ATPase pump. The sodium channel has been studied using a tritiated derivative of tetrodotoxin; the sodium pump has been studied using tritiated ouabain. Properties of interaction of tritiated tetrodotoxin and of tritiated ouabain with their respective receptors were observed in normal human skeletal muscle and in muscles of patients with myotonic muscular dystrophy and with lower motor neuron impairment.Levels of sodium pump and of sodium channels were measured at different stages of membrane purification. Microsomal fractions of normal human muscle have maximal binding capacities for tetrodotoxin of 230 fmol/mg of protein and of 7.4 pmol/mg of protein for ouabain.Dissociation constant for the complexes formed by the tetrodotoxin derivative and by ouabain with their respective receptors were 0.52 nM and 0.55 ,uM, respectively.In muscles from patients with myotonic muscular dystrophy, the maximal binding capacity for tetrodotoxin, i.e., the number of Na+ channels was found to be very similar to that found for normal muscle.The maximal binding capacity for ouabain, i.e., the number of Na+ pumps was three-to sixfold lower than in normal muscle. Dissociation constants for the com-

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The electrical properties of muscle fiber membranes in dystrophia myotonica and myotonia congenita.

Cited by 43 publications

References 24 publications

Cultured muscle from myotonic muscular dystrophy patients: altered membrane electrical properties.

Cultured muscle from myotonic muscular dystrophy patients: altered membrane electrical properties.

Cable parameters, sodium, potassium, chloride, and water content, and potassium efflux in isolated external intercostal muscle of normal volunteers and patients with myotonia congenita

Sodium Channel and Sodium Pump in Normal and Pathological Muscles from Patients with Myotonic Muscular Dystrophy and Lower Motor Neuron Impairment

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