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Biomedical subjects

S H Bryant

Publications and source records attributed to S H Bryant.

At least 73 records · Page 4Linked to original sources

Effect of calcium antagonist drugs on calcium currents in mammalian skeletal muscle fibers.

The calcium channel-inhibiting drugs diltiazem, verapamil and nitrendipine represent three general classes of organic calcium antagonists. In the present study, the effect of these drugs on calcium currents (ICa++) in rabbit sternomastoid muscle fibers was examined. ICa++ were recorded at room temperature using a vaseline gap voltage clamp. ICa++ measured had similar kinetics to those reported in rat skeletal muscle, were partially blocked by 0.5 mM CdCI2 and could be reduced by substitution of Mg++ for Ca++. Diltiazem reversibly blocked ICa++ in a concentration-dependent manner with the 50% inhibitory concentration (IC50) being 63 microM. Verapamil was slightly more potent with approximately 50% block of ICa++ occurring at 10 microM. In contrast, nitrendipine at concentrations from 1 to 10 microM had no blocking action on ICa++, even after 20 min of exposure. Thus, although Ca++ channels in mammalian skeletal muscle fibers are readily blocked by cadmium, diltiazem and verapamil, these channels appear to be insensitive to the dihydropyridine compound nitrendipine.

Animals↗

Effects of pulmonary function on mortality.

Survivorship data from a 24 year longitudinal study of 874 male volunteers in the Baltimore Longitudinal Study of Aging were used to assess the role of pulmonary function on total mortality. Even when age and smoking were considered, the ratio of forced expiratory volume in 1 sec to its predicted value was significantly associated with mortality from all causes. Individuals with poorer pulmonary function showed greater mortality during the follow-up period of this study. This relationship was also seen among never smokers in this sample, further supporting the hypothesis that impaired pulmonary function is itself a predictor of total mortality and may contribute to a number of disease processes.

Adolescent↗

The influence of inactivity on membrane resting conductances of rat skeletal muscle fibres undergoing reinnervation.

The role of activity in the maintenance of the normal component resting conductances of skeletal muscle fibres has been evaluated in vitro in rat extensor digitorum longus muscle during reinnervation from 2 to 40 days (a) after crushing of the peroneus nerve and (b) after local application of tetrodotoxin (TTX) to the crushed nerve. Whereas membrane conductances were regained after crushing alone, they were not completely restored when impulse propagation was blocked with TTX. It is concluded that nerve trophic factors are of primary importance in the control of muscular membrane conductances, and that transmission at the endplate and the muscle usage triggered by it have a minor but significant effect.

Animals↗

Diltiazem potentiates mechanical activity in mammalian skeletal muscle.

The calcium antagonist drug diltiazem produces a concentration dependent increase in twitch amplitude and a decrease in the mechanical threshold in mouse and rat skeletal muscle fibers in vitro. The greater potency of the d-cis isomer of diltiazem over the 1-cis isomer suggests that the effects of diltiazem are specific and may result from its binding to a specific receptor.

Animals↗

Isomyosin distribution in skeletal muscles of normal and myotonic goats.

Isoforms of myosin were examined in hindleg muscles isolated from normal and myotonic goats. The muscles studied were the soleus, gastrocnemius, gluteus accessorius, semitendinosus, semimembranosus, and adductor. The isomyosins were analyzed by pyrophosphate polyacrylamide gel electrophoresis. The relative proportions of slow and fast myosin isoforms present were determined by densitometric scanning of Coomassie Blue-stained gels. All muscles contained three fast myosin isoforms and either one or two slow myosin isoforms. In normal goat, the soleus and gastrocnemius, containing 70%-75% slow isomyosins, were representative of slow muscle. The semimembranosus, the semitendinosus, and the adductor, with more than 50% fast myosin, represented a predominantly fast muscle group. The gluteus accessorius, with approximately 45% fast myosin isoforms, was intermediate between the other two groups. In the myotonic goat, a consistent and significant increase in the proportion of fast isomyosins was observed for all the muscles studied. The largest change occurred in the gastrocnemius where the incremental increase in the percentage of fast isomyosins was over 30%. All the other muscles examined had incremental increases in fast isomyosin content which ranged from 16.1% to 22.0%. These results suggest that the abnormal action potential pattern of myotonia leads to a redistribution of the myosin isoforms.

Action Potentials↗

The toxic effects of clofibrate and its metabolite on mammalian skeletal muscle: an electrophysiological study.

Membrane electrical parameters of rat extensor digitorum longus muscles were analysed in vitro, with intracellular microelectrodes, after chronic treatment with clofibrate or after in vitro application of chlorophenoxyisobutyric acid, the in vivo metabolite of clofibrate. Clofibrate caused only a 38% decrease in the membrane chloride conductance while its metabolite induced a large decrease of chloride conductance and drastic changes in the excitability characteristics of the muscles sampled. The capability of clofibrate to induce two types of myotonia is discussed.

Action Potentials↗

Increased membrane permeability to chloride in Duchenne muscular dystrophy fibroblasts and its relationship to muscle function.

Previous studies have suggested an abnormality in Cl- metabolism in Duchenne muscular dystrophy (DMD) fibroblasts. In order to further characterize this abnormality, we have studied 36Cl- distribution and permeability in 11 DMD and 12 normal fibroblast lines. Under steady-state conditions Cl- efflux in fibroblasts is observed to be biphasic, revealing the presence of two major subcellular compartments. Each compartment contains approximately half of the cellular Cl-. The faster of the two observed efflux components is significantly higher in DMD than in control fibroblasts (P less than 0.001). To determine the results of a similar increase in Cl- permeability on skeletal muscle action potentials, we have simulated the effects of increased Cl- conductance on muscle by using a computer model. Effects on the simulated action potential include lower rates of membrane depolarization, lower overpotential, longer duration, and lower input resistance. These effects are similar to those actually observed in DMD muscle.

Action Potentials↗

Sodium currents in human skeletal muscle fibers.

Sodium currents from human external intercostal muscle fibers were recorded using the Hille-Campbell voltage clamp method. Sodium currents are analyzed in terms of the m and h parameters of the Hodgkin-Huxley model. The results indicate that the kinetics and voltage dependence of sodium currents in human skeletal muscle fibers are very similar to those reported in rat fibers.

Humans↗

Gene flow and the geographical distribution of a molecular polymorphism in Drosophila pseudoobscura.

This paper discusses the relation between the geographical distribution of an enzyme polymorphism and population structure in Drosophila pseudoobscura. California populations of this species living in very different montane and lowland habitats separated by several kilometers are similar to each other in the frequency of an esterase allele. Previous estimates suggest that gene flow is too limited to account for this homogeneity of genetic structure, so that it must reflect some balancing force of natural selection. We slow, however, that dispersal over unfavorable habitats is much greater than earlier supposed. Isolated populations of D. pseudoobscura separated by 15 km from other populations are subject to large amounts of immigration. This is shown by changes in the seasonal abundance of this species and in the annual pattern of lethal alleles in such populations. The genetic structure of an experimentally perturbed isolated population in an oasis returned to normal within a single year, suggesting that such populations are ephemeral and that the oasis is subject to annual recolonization by distant migrants. Direct assessment of marked flies shows that they can move at least 10 10 km in 24 hours over a desert. Such extensive gene flow may help explain the distribution of the esterase allele, and is relevant to the high level of molecular polymorphism and its general lack of geographic differentiation throughout the range of D. pseudoobscura.

Alleles↗

Dependence of membrane potential on extracellular ionic concentrations in myotonic goats and rats.

Intracellular potassium concentration([K]i) and the resting sodium-to-potassium permeability ratio (alpha = PNa/PK) were determined by recording resting potentials at 25 degrees C in six solutions with variable potassium concentrations, constant [K+] + [Na+], and constant [K+] X [Cl-] product and fitting the results by nonlinear least squares to the Goldman-Hodgkin-Katz equation. Fits to models including chloride permeability terms suggest that chloride is in Donnan equilibrium in the muscles studied. External intercostal muscle was biopsied from anesthetized normal goats and goats with hereditary myotonia. In normal goat muscle, alpha was 0.012 +/- 0.001 (mean +/- SE, n = 11), and [K]i was 133 +/- 6 mM (n = 9); myotonic goat muscle did not differ from this. Extensor digitorum longus (EDL) muscle was removed from anesthetized male Wistar rats and from like rats pretreated with a single large dose of 20,25-diazacholesterol (DAC). In normal rat EDL, alpha was 0.019 +/- 0.002 (n = 12), and [K]i was 142 +/- 4 mM (n = 12). In the 16-day DAC-treated rats, alpha was significantly reduced (P < 0.002) to 0.010 +/- 0.002 (n = 8), and [K]i was slightly reduced by DAC. It is concluded that DAC reduced PNa in rat fibers. Tetrodotoxin at 5 microM did not affect either parameter in the rats.

Animals↗

Clan lethals and inter-year allelism in Death Valley Drosophila pseudoobscura.

A chromosome 2 lethal allelism rate of about 3% found in the 1974 population of D. pseudoobscura in Death Valley, California. This rate was significantly higher than allelism rates in other Southern California populations. The Death Valley population was sampled again in 1975 and 1977, with allelism rates of 1% and 0.5%, respectively. In 1974, several lethals were in high frequencies (about 1%), a pattern that reappeared in 1975 and 1977. However, none of the lethals in high frequency one year was in high frequency another year; the particular lethal alleles present in this ephemeral population appear to be due to their random presence in the flies which refound the population every winter. The results for the Death Valley population are compared with a Japanese population of D. melanogaster in which lethals in high frequency one year also in high frequency in succeeding years and with earlier work on chromosome 3 of D. pseudoobscura, which showed a lower lethal frequency and higher allelism rate.

Alleles↗

Suppression of myotonia in dystrophic chicken muscle by phenytoin.

We describe myotonic electromyographic activity in muscles of genetically dystrophic chickens and show that this activity is antagonized in vivo by doses of phenytoin (DPH) that improve righting ability. To test the possibility that the in vivo effects of DPH can be accounted for by a direct action on skeletal muscle we studied posterior latissimus dorsi fibers in vitro at 23 degrees C with intracellular microelectrodes. Compared to normal fibers, fibers from untreated dystrophic chicks had larger diameters, increased membrane capacitance, longer latencies at rheobase, and a greater tendency to fire repetitively in response to direct stimulation. DPH (10 or 50 micrograms/ml in the bath solution) decreased latencies at rheobase and repetitive firing in fibers from untreated chicks. In DPH-free solution fibers from dystrophic chicks treated chronically with DPH were still abnormal with respect to latencies at rheobase and ease of repetitive firing. The data support the hypothesis that abnormalities of membrane electrical properties are major features of dystrophic chicken muscles and furthermore, show that DPH suppresses, but does not abolish, these abnormalities.

Animals↗