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...

+ oxoglutarate),,, : malatein catalysed by the oxoglutarate carrier of rat-heart mitochondria have been studied under conditions where internal and external substrates may be varied.It is shown that contrary to external oxoglutarate which induces a conformational change of the translocator subunit to which it binds, external malate does not induce conformational changes during its binding and is a Michaelian substrate.The study of the effect of external malate on the rate of oxoglutarate uptake shows that external malate and external oxoglutarate are competitive.External oxoglutarate affects the catalytic rate constant of malate uptake in a modulated way. After substrate binding, the exchange reaction between an external dicarboxylate and an internal dicarboxylate is accompanied by conformational changes. The particular form of the rate equation strongly suggests that during a first step the external substrate bound to an external binding subunit at the external surface of the membrane, and the internal substrate bound to an internal binding subunit at the internal surface of the membrane, are transferred to a catalytic subunit (channel?) deeper in the membrane. Two models, one with a single channel, and the other with several associated channels, are proposed.It is demonstrated that a binding subunit which has transferred its substrate to a catalytic subunit is left in a conformation which does not depend on the substrate that has 'passed through it'. It is also demonstrated that all the catalytic subunits are identical. These theoretical dcductions allow a simple description of the complicated effect that external oxoglutarate has on the rate of malate uptake.The fact that all the external binding subunits arc equivalent regarding external malate binding and that all the catalytic subunits are identical support the view that the mitochondria1 preparation contains a single species of oxoglutarate translocator and not an isozymic mixture.The oxoglutarate translocator present in rat-heart mitochondria [I] is located in the inner membrane and performs one-to-one exchanges between an external and an internal dicarboxylate anion as shown explicitly in [2].The oxoglutarate translocator is a component of the malate-aspartate shuttle which transfers reducing equivalents produced in the cytosol to the respiratory chain located in the mitochondria. This shuttle is not only the main transfer device in heart but is also strictly necessary in working heart preparations metabolizing glucose, since aminooxyacetate, an inhibitor of the transamination steps of the shuttle, causes leftventricular failure, decreases myocardial respiration and increases lactate production [3]. By recycling the glycolytic NADH, the malate-aspartate shuttle thus protects pyruvate from reduction allowing its vital oxidation by the Krebs cycle.The glycolytic activity in the sarcoplasm and the oxidative phosphorylation in the mitochondria are linked by transmcmbrane translocators : the pyruvate, adenine-nucleotide, oxogluAhhreviatlon.s. Mal, malate; OG...

We questioned whether polyamines coming from the diet or produced by intestinal microflora or by intracellular metabolism influence intestinal functions. Therefore, we compared pathogen-free rats and germ-free rats receiving a diet with low polyamine content and either treated or not treated with difluoromethylornithine (DFMO) and/or methylglyoxal bis (guanylhydrazone) (MGBG). Wet weight, protein content, DNA content, sucrase (EC3.2.1.48), maltase (EC3.2.1.20) and lactase (EC 3.2.1.23) specific activities, amounts of putrescine, spennidine and spemine were measured in the mucosa of the proximal and distal intestine. Body weight was also determined. Rats without microflora had a higher specific activity of maltase and higher amounts of spermidine and spermine but lower lactase specific activity than pathogen-free animals; the low-polyamine diet given to gem-free rats had little effect on the functional variables measured (decrease of maltase and lactase specific activities) and did not modify the amounts of polyamines. DFMO and/or MGBG administered to germ-free rats receiving a low-polyamine diet induced modifications of most of the variables studied. Body weight and wet weight of proximal and distal intestine decreased, disaccharidase specific activities decreased, and amounts of polyamines changed according to the inhibitor used. Thus, our results showed that the deprivation of polyamine supply from microflora or from the diet failed, under our experimental conditions, to affect the intestinal properties analysed but exogenous and endogenous polyamine restriction altered general properties of the organism as well as intestinal functions.