Cyclic adenosine-3',5'-monophosphate content of the brain in conditions of extreme stimulation]

The content of brain cAMP was investigated under conditions of electric stimulation of immobilized rats which resulted in the development of reflex dystrophies of the internal organs. There was found a pronounced decrease in the amount of cAMP in the rat brain which developed 15 minutes after the beginning of extreme stimulation and remaained at the same low level for 3 hours after the electrical irritation. Reduction of the cAMP level was probably connected with noradrenaline and other biologically-active amine deficiency in the brain under conditions of extreme stimulation.     

Involvement of inositol 1,4,5-trisphosphate in nicotinic calcium responses in dystrophic myotubes assessed by near-plasma membrane calcium measurement

In skeletal muscle cells, plasma membrane depolarization causes a rapid calcium release from the sarcoplasmic reticulum through ryanodine receptors triggering contraction. In Duchenne muscular dystrophy (DMD), a lethal disease that is caused by the lack of the cytoskeletal protein dystrophin, the cytosolic calcium concentration is known to be increased, and this increase may lead to cell necrosis. Here, we used myotubes derived from control and mdx mice, the murine model of DMD, to study the calcium responses induced by nicotinic acetylcholine receptor stimulation. The photoprotein aequorin was expressed in the cytosol or targeted to the plasma membrane as a fusion protein with the synaptosome-associated protein SNAP-25, thus allowing calcium measurements in a restricted area localized just below the plasma membrane. The carbachol-induced calcium responses were 4.5 times bigger in dystrophic myotubes than in control myotubes. Moreover, in dystrophic myotubes the carbachol-mediated calcium responses measured in the subsarcolemmal area were at least 10 times bigger than in the bulk cytosol. The initial calcium responses were due to calcium influx into the cells followed by a fast refilling/release phase from the sarcoplasmic reticulum. In addition and unexpectedly, the inositol 1,4,5-trisphosphate receptor pathway was involved in these calcium signals only in the dystrophic myotubes. This surprising involvement of this calcium release channel in the excitation-contraction coupling could open new ways for understanding exercise-induced calcium increases and downstream muscle degeneration in mdx mice and, therefore, in DMD.     

Absence of Non-Thermal Microwave Effects on the Function of Giant Nerve Fibers

Functioning of the giant axon of the isolated earthworm ventral nerve cord was examined during exposure to 6.45 GHz microwaves. We used continuous wave and pulsed irradiation, either synchronized with stimuli or asynchronous, lasting for 10–50 min at specific absorption rate from 30 to 230 W/kg. Action potential (AP) conduction velocity and the capability of nerve fiber to answer long-lasting high-frequency stimulation served as indices of microwave effect. Under some experimental conditions the nerve appeared to have extreme sensitivity to subtle temperature changes, induced by irradiation, but no non-thermal microwave effects were detected.     

Spontaneous regeneration of older dystrophic muscle does not reflect its regenerative capacity

Young dystrophic (dy) murine muscle is capable of "spontaneous" regeneration (i.e., regeneration in the absence of external trauma); however, by the time the mice are 8 weeks old, this regeneration ceases. It has been suggested that the cessation of regeneration in dystrophic muscle may be due to exhaustion of the mitotic capability of myosatellite cells during the early stages of the disease. To test this hypothesis, orthotopic transplantation of bupivacaine treated, whole extensor digitorum longus muscles has been performed on 14 to 16-week-old 129 ReJ/++ and 129 ReJ/dydy mice. The grafted dystrophic muscle is able to produce and maintain for 100 days post-transplantation 356 +/- 22 myofibers, a number similar to that found in age-matched dystrophic muscle. The ability of old dystrophic muscle to regenerate subsequent to extreme trauma indicates that the cessation of "spontaneous" regeneration is due to factor(s) other than the exhaustion of mitotic capability of myosatellite cells. Moreover, there is no significant difference in myosatellite cell frequencies between grafted normal and dystrophic muscles (100 days post-transplantation). Myosatellite cell frequencies in grafted muscles are similar to those in age-matched, untraumatized muscles. While grafting of young dystrophic muscle modifies the phenotypic expression of histopathological changes usually associated with murine dystrophy, grafts of older dystrophic muscle show extensive connective-tissue infiltration and significantly fewer myofibers than do grafts of age-matched normal muscle. As early as 14 days post-transplantation, it is possible to distinguish between grafts of old, normal and dystrophic muscles. It is suggested that the connective tissue stroma, present in the dystrophic muscle at the time of transplantation, may survive the grafting procedure.     

Chronic AMPK stimulation attenuates adaptive signaling in dystrophic skeletal muscle

In the present study, we evaluated how a pharmacologically induced phenotype shift in dystrophic skeletal muscle would affect subsequent intracellular signaling in response to a complementary, adaptive physiological stimulus. mdx mice were treated with the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR; 500 mg·kg(-1)·day(-1)) for 30 days, and then one-half of the animals were subjected to a bout of treadmill running to induce acute AMPK and p38 MAPK signaling. The mRNA levels of phenotypic modifiers, including peroxisome proliferator-activated receptor-δ (PPARδ), PPARγ coactivator-1α (PGC-1α), receptor interacting protein 140 (RIP 140), and silent information regulator two ortholog 1 (SIRT1) were assessed in skeletal muscle, as well as the expression of the protein arginine methyltransferase genes PRMT1 and CARM1. We found unique AMPK and p38 phosphorylation and expression signatures between dystrophic and healthy muscle. In dystrophic skeletal muscle, treadmill running induced PPARδ, PGC-1α, and SIRT1 mRNAs, three molecules that promote the slow, oxidative myogenic program. In the mdx animals that received the chronic AICAR treatment, running-elicited AMPK and p38 phosphorylation was attenuated compared with vehicle-treated mice. Similarly, acute stress-evoked expression of PPARδ, PGC-1α, and SIRT1 was also blunted by chronic pharmacological AMPK stimulation. Skeletal muscle PRMT1 and CARM1 protein contents were higher in mdx mice compared with wild-type littermates. The acute running-evoked induction of PRMT1 and CARM1 mRNAs was also attenuated by the AICAR treatment. Our data demonstrate that prior pharmacological conditioning is a salient determinant in how dystrophic muscle adapts to subsequent complementary, acute physiological stress stimuli. These results provide insight into possible therapeutic applications of synthetic agonists in neuromuscular diseases, such as during chronic administration to Duchenne muscular dystrophy patients.     

Stress and muscular dystrophy: a genetic screen for dystroglycan and dystrophin interactors in Drosophila identifies cellular stress response components

In Drosophila, like in humans, Dystrophin Glycoprotein Complex (DGC) deficiencies cause a life span shortening disease, associated with muscle dysfunction. We performed the first in vivo genetic interaction screen in ageing dystrophic muscles and identified genes that have not been shown before to have a role in the development of muscular dystrophy and interact with dystrophin and/or dystroglycan. Mutations in many of the found interacting genes cause age-dependent morphological and heat-induced physiological defects in muscles, suggesting their importance in the tissue. Majority of them is phylogenetically conserved and implicated in human disorders, mainly tumors and myopathies. Functionally they can be divided into three main categories: proteins involved in communication between muscle and neuron, and interestingly, in mechanical and cellular stress response pathways. Our data show that stress induces muscle degeneration and accelerates age-dependent muscular dystrophy. Dystrophic muscles are already compromised; and as a consequence they are less adaptive and more sensitive to energetic stress and to changes in the ambient temperature. However, only dystroglycan, but not dystrophin deficiency causes extreme myodegeneration induced by energetic stress suggesting that dystroglycan might be a component of the low-energy pathway and act as a transducer of energetic stress in normal and dystrophic muscles.     

Defect in regulation of membrane transport of monosaccharides in dystrophic muscle.

The penetration of a nonmetabolized glucose analogue, 3--O-methyl-D-glucose, across the plasma membranes of tissues from dystrophic mice and cardiomyopathic (dystrophic) hamsters has been compared with that of normal controls. Under basal conditions the penetration of test sugar was similar in lens and diaphragm of normal and dystrophic 129/ReJ mice. Stimulation of sugar transport by 2,4-dinitrophenol did occur in normal but not in dystrophic diaphragm. A submaximal concentration of insulin had a more variable effect in dystrophic than in normal muscle while a supramaximal concentration of the hormone increased the uptake of the glucose analogue to an equal extent in the two tissues. In the BIO 14.6 strain of cardiomyopathic hamsters, uncoupling of oxidative phosphorylation did not increase sugar transport in extensor digitorum longus muscles, while the normal effect was observed in dystrophic soleus and in both these muscles of the random bred controls. The absence of an effect by a condition simulating anoxia suggests that in dystrophy, certain muscles are unable to accelerate the entry of glucose when this is required.     

Contrasts between dystrophic and clearwater lakes in the long‐term effects of acidification on cladoceran assemblages

1. Most studies on zooplankton responses to acidification have focused on clearwater lakes with a dramatic acidification history. The role of dissolved organic carbon (DOC) in moderating zooplankton responses to acidification in naturally acidic, dystrophic lakes is less well understood and is partially impeded by a lack of baseline data. 2. Cladocera leave identifiable remains preserved in lake sediments that can be used to provide information on pre‐industrial species assemblages and their responses to environmental stressors such as acidification. Therefore, we used palaeolimnological approaches to track cladoceran assemblage responses to acidification since c.1850 (inferred from sedimentary diatom assemblages) in three acidified lakes in Kejimkujik National Park (Nova Scotia, Canada) that differ markedly in DOC content. These include two highly dystrophic lakes (Kejimkujik and Pebbleogittch lakes), and one clearwater lake (Beaverskin Lake). 3. In dystrophic Pebbleogittch Lake, an increase in the acid‐tolerant, jelly‐clad, pelagic taxon Holopedium glacialis occurred coincident with diatom‐inferred pH (DI‐pH) declines, but no other notable cladoceran assemblage shifts occurred. Similarly, Cladocera assemblages did not appear to respond to lakewater acidification in dystrophic Kejimkujik Lake. 4. In contrast, in the clearwater Beaverskin Lake, several observed shifts in cladoceran assemblage corresponded to DI‐pH declines, including an increase in the proportion of littoral taxa and an increase in Hill’s N2 species diversity. This may indicate increased water clarity as a result of acidification‐related decreases in DOC, which may have enhanced growth of emergent aquatic macrophytes and improved visibility for planktivorous fish, leading to increased predation on pelagic taxa. Species shifts within the littoral assemblage of Beaverskin Lake may reflect the differing tolerances of littoral taxa to low pH and aluminium toxicity. 5. Overall, our results suggest that cladoceran assemblages in naturally acidic, dystrophic lakes may be resilient against additional pH declines related to industrial emissions of acidifying agents, as dystrophic lakes are less vulnerable to increased aluminium toxicity and acidification‐induced increases in water clarity and often have a pre‐industrial cladoceran assemblage already adapted to acidic conditions.     

Skeletal muscle protein and amino acid metabolism in hereditary mouse muscular dystrophy. Accelerated protein turnover and increased alanine and glutamine formation and release

Interactins between skeletal muscle protein and amino acid metabolism were investigated using C57BL and 129ReJ mice with hereditary muscular dystrophy. On incubation, hind limb muscle preparations from dystrophic mice released large quantities of amino acids, particularly alanine and glutamine which were increased 70% and 40% compared to muscles from carrier or control mice. The increased alanine release did not result from altered alanine oxidation to CO2 or reincorporation into protein. Alanine and glutamine formation from added amino acids were equal with dystrophic and control muscles. Incorporation in vitro of leucine, alanine, and glutamate into proteins of dystrophic muscle was 3- to 7-fold greater than control muscle, and the incorporation in vivo of [3H]- or [14C]arginine into muscle proteins was greater in extent and earlier in time with dystrophic as compared to control muscle. Proteins were also labeled in vivo using [guanido-14C]arginine. On incubation of these muscles in vitro, a 100% greater loss of label from protein was observed with dystrophic as compared to control preparations, and the appearance of label in the media was correspondingly increased. Sodium dodecyl sulfate-gel electrophoresis of dystrophic skeletal muscle showed numerous protein bands to be reduced in density, but autoradiographic studies demonstrated that these same bands were more highly labeled in vitro by [35S]methionine in dystrophic than in control muscle. Although insulin stimulation of glucose uptake was markedly blunted in dystrophic muscle, insulin inhibited alanine and glutamine release equally from both control and dystrophic muscle. These data indicate that alanine and glutamine formation and release are increased in hereditary mouse muscular dystrophy. An accelerated degradation and an increased resynthesis of many muscle proteins were also observed in dystrophic compared to control animals. This increased proteolysis may account for the increased alanine and glutamine formation in dystrophic muscle.     

Effect of antibiotics on the structure and function of the ovaries

Streptomycin, penicillin, levomycetin, florimycin, cycloserin, erythromycin, sekazin, novobiocin, tetracyclines and neomycins had a stimulating effect on the sexual organs of the tests animals during the 1st decade of their administration. With long-term use some of the drugs induced dystrophic changes in the ovary. The signs of stimulation in the ovary were evident from increased activity of the oxidation-reduction enzymes in the inner membrane of the follicles and the interstitial cells of the stroma, as well as in an increase in the number of the maturating follicles. With long-term long use of erythromycin, sekasin or novobiocin, disappearance of the primordial follicles, an increase in the number of the atretic follicles and death of the ovocytes in the mature follicles were observed in the ovary.     

Growth factor-dependent proliferation and invasion of muscle satellite cells require the cell-associated fibrinolytic system

The process of muscle regeneration in normal and dystrophic muscle depends on locally produced cytokines and growth factors and requires the activity of the urokinase plasminogen activator/urokinase plasminogen activator receptor/plasminogen activator inhibitor-1 system. In this study we tested the effect of basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and transforming growth factor-beta (TGFbeta) on the fibrinolytic pattern of normal and dystrophic satellite cells, their mitogenic and motogenic activities and the dependence of such activities on the cell-associated fibrinolytic system. We have observed that the urokinase plasminogen activator (u-PA) receptor is weakly upregulated by bFGF in normal satellite cells, while it is strongly up-regulated by TGFbeta, mainly in dystrophic myoblasts. bFGF up-regulated u-PA in both normal and dystrophic myoblasts grown in primary culture, while a striking down-regulation was observed with TGFbeta. TGFbeta was the only growth factor able to exceptionally up-regulate plasminogen activator inhibitor-1 (PAI-1), mainly in dystrophic satellite cells. HGF did not show any activity on the fibrinolytic system. Proliferation and invasion into Matrigel matrices of normal and dystrophic cells occurred regardless of the growth factor-dependent regulation of the fibrinolytic system. Nevertheless, each growth factor required the efficiency of the constitutive cell-associated fibrinolytic system to operate, as shown by impairment of growth factor activity with antagonists of u-PA and of its receptor. Noteworthy, TGFbeta induced a dose-dependent increase of Matrigel invasion only in dystrophic myoblasts. Since TGFbeta-challenged dystrophic myoblasts undergo an exceptional up-regulation of the receptor and of PAI-1, we propose the possibility that the TGFbeta-induced fibrinolytic pattern (low urokinase plasminogen activator, high receptor and high PAI-1) may be exploited to promote survival and spreading of transplanted engineered myoblasts in Duchenne muscular dystrophy.     

Enzymatic activity of dystrophic chicken sarcoplasmic reticulum

We have isolated sarcoplasmic reticulum from normal and dystrophic chicken muscle, using an improved isolation procedure. Dystrophic sarcoplasmic reticulum has a reduced level of calcium-sensitive ATPase activity, phosphoenzyme formation, and steady-state calcium transport. Anion-stimulated calcium transport by dystrophic sarcoplasmic reticulum is also reduced when measured under the proper conditions, and dystrophic sarcoplasmic reticulum shows no alteration in calcium efflux rate. Active calcium phosphate loading of the normal and dystrophic sarcoplasmic reticulum preparations indicates that a reduced percentage jof the dystrophic vesicles are capable of active calcium transport. The loaded dystrophic sarcoplasmic reticulum vesicles exhibit the same relative reductions in enzymatic activity as the starting sarcoplasmic reticulum preparations. However, the enzyme activities of normal and dystrophic sarcoplasmic reticulum are similar in the presence of detergent and exogenous phospholipid. On the basis of these results, we suggest that the lipid microenvironment of the dystrophic enzyme is altered.     

Effects of the sex-linked dwarf gene (dw) on the expression of the muscular dystrophy gene (am) in chicken.

The sex-linked dwarf gene (dw) was introduced into companion muscular dystrophic (am) and nondystrophic (Am+) New Hampshire chicken lines to investigate influences of the dwarf gene on breast muscle weights, muscle fiber area, and the histological expression of muscular dystrophy. Dystrophic and nondystrophic chickens within dwarf or nondwarf genotypes were similar in body and carcass weights. Pectoralis and supracoracoideus muscle weights (as a percentage of adjusted carcass weight) were similar in nondystrophic dwarf and nondwarf males and females. In addition, pectoralis weight was similar in dystrophic dwarf males and dystrophic nondwarf males and females. However, pectoralis weight was significantly smaller in dystrophic dwarf females than in dystrophic nondwarf females, whereas supracoracoideus weight was significantly larger in dystrophic dwarf males than in dystrophic nondwarf males. Supracoracoideus weight was similar in dystrophic dwarf males and females and dystrophic nondwarf females. Pectoralis muscle fiber area was influenced by sex and by dwarf and dystrophy genotype. Muscle fiber area was larger in females than in males, smaller in dwarfs than in nondwarfs, and smaller in dystrophic than in nondystrophic muscles. Muscle fiber degeneration and adipose infiltration was more extensive in dystrophic than in nondystrophic females and males, and it was more advanced in dwarfs than in nondwarfs. Excessive acetylcholinesterase staining patterns were characteristic of dystrophic muscle in both dwarf and nondwarf genotypes. Nondystrophic and dystrophic dwarf male and female chickens are comparable substitutes for nondwarfs as biomedical models with respect to pectoralis histology, acetylcholinesterase staining pattern, and pectoralis muscle hypertrophy.     

Synthesis of retinoids by human retinal epithelium and transfer to rod outer segments.

In order to gain an insight into the pathogenesis of mouse muscular dystrophy, we investigated the natural suppressor serine tRNA. The natural suppressor seryl-tRNA was distinguished from the other seryl-tRNAs on the basis of its specific property of being converted into phosphoseryl-tRNA by a tRNA kinase. On a wet-weight basis, the content of total tRNA in dystrophic muscles was 47% of that in normal muscles. Although the serine-accepting activities of tRNA were similar in muscles of 3-month-old dystrophic and normal mice, the ratio of [32P]phosphoseryl-tRNA (suppressor tRNA) to the total serine tRNA was significantly enhanced in dystrophic muscles compared with that in normal muscles. This high content of suppressor tRNA in dystrophic muscles was further confirmed by dot-blot hybridization experiments with the DNA probes CGTAGTCGGCAGGAT and CGCCCGAAAGGTGGAA for major tRNA(IGASer) and suppressor tRNA respectively. At the early postnatal age of 3 weeks, when only a week had elapsed since the first manifestation of the dystrophic symptom (hindleg dragging), the ratio of suppressor tRNA to major tRNAs in dystrophic hindleg muscles was abnormally increased. Thereafter it decreased with age in normal mice but remained almost unchanged in dystrophic mice. Consequently, at 3 months old, it was 1.7 times higher in dystrophic than in normal mice. The suppressor tRNA is now accepted to play a role in the synthesis of glutathione peroxidase. The present study showed that the content of this enzyme was abnormally elevated in dystrophic mice. Previously we had demonstrated that the docosahexaenoic (C22:6) acid content in phospholipids was decreased, possibly resulting from the enhanced oxidative milieu caused by the dystrophic condition. Thus far, the findings suggest that an increase in the contents of suppressor tRNA and glutathione peroxidase in dystrophic muscle may have been secondarily induced by such a highly oxidative state in the dystrophic condition. However, it is difficult to exclude the possibility that the natural suppressor tRNA plays a primary role in the pathogenesis of muscular dystrophies.     

The effect of Ca-transport inhibitors on the excitability of the pregnant and post partum rabbit uterus

To continue an earlier study, a total of 54 uterine strips were excised from 25 days pregnant and post partum rabbits. These muscles were examined under a variety of experimental conditions to further define functionally their “activator-Ca” (A-Ca) which couples excitation with contraction under these two extreme regulatory states of the uterus. As in earlier studies, increasing the stimulus strength in graded steps from 2 to 80 V/5 cm revealed two distinct “peaks” of excitability, one at ～12 V/5 cm and another at ～60 V/6 cm, separated by a zone of inhibition. Knowing that effective “first peak” stimulation demands intact membrane function and the availability of A-Ca, while the “second peak” stimulation probably bypasses the membrane process and activates the contractile system directly by mobilizing Ca bound to intracellular structures, the effects on the strength-tension curve of normal and Ca-free KRB, excess KCl, Verapamil, Ruthenium-red and MnCl₂ were examined. These studies exposed again the different states of the A-Ca in the uteri of pregnant and post partum rabbits, which partly explain the functional differences of the myometrium under these two extreme regulatory conditions.     

Induction of Curvature in Maize Roots by Calcium or by Thigmostimulation : Role of the Postmitotic Isodiametric Growth Zone

We examined the response of primary roots of maize (Zea mays L. cv Merit) to unilateral application of calcium with particular attention to the site of application, the dependence on growth rate, and possible contributions of thigmotropic stimulation during application. Unilateral application of agar to the root cap induced negative curvature whether or not the agar contained calcium. This apparent thigmotropic response was enhanced by including calcium in the agar. Curvature away from objects applied unilaterally to the extreme root tip occurred both in intact and detipped roots. When agar containing calcium chloride was applied to one side of the postmitotic isodiametric growth zone (a region between the apical meristem and the elongation zone), the root curved toward the side of application. This response could not be induced by plain agar. We conclude that curvature away from calcium applied to the root tip results from a thigmotropic response to stimulation during application. In contrast, curvature toward calcium applied to the postmitotic isodiametric growth zone results from direct calcium-induced inhibition of growth.     

Palmityl-CoA synthetase activity in the muscle of dystrophic mice.

Palmityl-CoA synthetase activity (acid CoA ligase (AMP), E C 6.2.1.3.) was determined using the radioassay method. The rate of formation of palmityl-CoA under the optimal conditions established was 20 nmoles per mg protein per min for mitochondria and 5.8 nmoles for the 9000 × g supernatant. The activity of palmityl-CoA synthetase in mitochondria from skeletal muscle of dystrophic mice was not significantly different from that obtained in normal littermate controls, whereas the activity of this enzyme in the 9000 × g supernatant fraction from dystrophic muscle preparation was found to be significantly higher than for the corresponding controls. It is concluded that the previously observed decrease in palmitate-1-¹⁴C oxidation in dystrophic muscle mitochondria was not due to a defect in the activation of palmitic acid.     

Apoptosis may contribute to false-positive results in the in vitro micronucleus test performed in extreme osmolality, ionic strength and pH conditions

Conditions in which clastogens produce positive responses have been increasingly challenged, and several situations have been described in which clastogenic responses would be considered not to be relevant. For example, extreme culture conditions lead to high variations of pH, osmolality or ionic strength. Apoptosis is induced in extreme culture conditions and contributes to false-positive results in the in vitro micronucleus test performed with CTLL-2 cells. These cells can enter apoptosis when exposed to apoptosis stimuli or after IL-2 deprivation, whereas the CTLL-2 Bcl2 cell line is protected from apoptosis due to the over-expression of the apoptosis inhibitor Bcl2 in bcl2-transfected CTLL-2 cells. The two cell lines were treated in extreme culture conditions of either pH or osmolality or were submitted to high ionic strength. The apoptosis level was measured in parallel with the in vitro micronucleus test using the annexin V-FITC method. Data obtained in the two cell lines suggested that apoptosis caused by extreme culture condition induces the formation of micronucleated cells, which leads to false-positive results in the in vitro micronucleus test.     

Evidence that the actin site is impaired by Ca2+-activated degradation of the heavy chain of dystrophic myosin

At pathophysiological concentrations of Ca²⁺, the heavy chain of dystrophic myosin was degraded by an endogenous protease. This was not the case for normal myosin. However, normal myosin was a substrate of Ca²⁺-activated neutral protease (CAF) from platelets. This indicated that the endogenous protease in preps of dystrophic myosin was CAF. The pathophysiological effect of heavy chain degradation was restricted to the actin site. Under Vmax conditions hydrolytic activities remained within the normal range, whereas the Kapp of actin for myosin increased 3-fold following extensive heavy chain degradation of dystrophic myosin. Removal of those heavy chain fragments which were soluble at low inoic strength restored Kapp to normal levels.     

The Effect of Variations in the Intra- and Extracellular Ion Concentrations upon the Electrical Activity of Normal and Dystrophic Mouse Skeletal Muscle

The resting and action potentials of the m. gastrocnemii of normal and dystrophic mice have been measured in vitro, under various conditions of the ionic environment. The observed effects are consistent with the view that, when equilibrium is established between internal and external ionic concentrations, the resting potential is determined very largely, and perhaps entirely, by the gradient of K ions. Action potentials are associated with a greatly increased Na conductance in this as in other excitable tissues. No differences in electrical activity between normal and dystrophic muscle cells could be established.