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

Abstract

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...

The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment

“…In myotonia congenita, the enhanced excitability is due to reduced sarcolemmal chloride conductance and was initially demonstrated in muscles of myotonic goats (Lipicky et al, 1966;Bryant., 1969) and later in humans (Lipicky et al, 1971). Compared with other excitable cells, skeletal muscle has an unusually high chloride conductance, accounting for up to 85% of the resting membrane conductance .…”

New Classification and Treatment for Myotonic Disorders

“…From these results it is comfirmed that myotonia occurs even if the neuromuscular junction is blocked and the t-system is disrupted: therefore, myotonia is elicited by muscle membrane abnormality. Then in 1971, Lipicky et al (5) performed intracellular recording of the muscle fibers and found that the membrane resistance of the muscle fibers obtained from myotonia congenita is increased as much as 2.2 times more than normal muscle membrane resistance. Since 80% of membrane conductance is due to Cl conductance, Lipicky et al considered that the increased membrane resistance of the myotonic muscle has decreased Cl conductance.…”

The Effect of Dehydroepiandrosterone Sulfate (DHEAS) on Myotonia: Intracellular Studies

“…The mechanism of action is unknown. In myotonia congenita, Lipicky and Bryant (4) clarified increased muscle membrane resistance due to decreased Cl conductance and later, the genetic abnormalities of Cl channel were clarified. The genetic basis for myotonic dystrophy is expansion of CTG repeats located in the 3'untranslated region of myotonic dystrophy protein kinase (DMPK) (5).…”