Responsiveness of normal and dystrophic avian muscle to acetylcholine, carbamylcholine and d-tubocurarine.

1. The responsiveness of dystrophic avian muscle to acetylcholine may be altered due to reported elevated acetylcholinesterase activity. 2. To test this hypothesis, the responsiveness of normal and dystrophic muscle in vivo to intra-arterial injection of acetylcholine, carbamylcholine and d-tubocurarine was compared. 3. Results showed that dystrophic muscle was less responsive to acetylcholine, more responsive d-tubocurarine and equally responsive to carbamylcholine when compared to normal suggesting enhanced acetylcholine hydrolysis occurs in vivo in dystrophic avian muscle.

Electrophysiologic differences between normal and dystrophic avian muscle.

In the avian model of muscular dystrophy, electrophysiologic studies have shown alterations in the action potential characteristics of dystrophic muscle in vitro, supporting the notion that a membrane defect exists in avian dystrophy. As neurogenic and vascular etiologies have also been proposed, we examined the characteristics of action potentials recorded in a novel in vivo preparation of the extensor digitorum communis muscle in 8-week-old normal and dystrophic chickens. To facilitate intracellular recording, dantrolene sodium was used to attenuate the muscle twitch. Results showed that although the resting membrane potential, action potential amplitude and the action potential maximum rate of rise were similar in normal and dystrophic cells, the action potential duration at half the maximum amplitude was increased in dystrophic cells. This observation has not been previously reported for dystrophic avian muscle and suggests that a defect in the sarcolemmal potassium conductance is an early change in dystrophic avian muscle.

Effects of noradrenaline, serotonin, and selected antagonists on the vascular smooth muscle of normal and dystrophic chickens.

The pathogenesis of the human muscular dystrophies is unknown, and several competing hypotheses have been proposed. The vascular hypothesis states that muscle fibre necrosis occurs in dystrophy as a result of transient muscle ischemia. Although abnormalities of the vascular system may be demonstrated in dystrophy, their role in pathogenesis remains obscure. The responses to serotonin (5-HT) and noradrenaline (NA) were examined in isolated ischiatic artery preparations from normal and genetically dystrophic chickens. The tension generated in response to 5-HT was greater in arteries from normal chickens than in arteries from dystrophic chickens, whereas responses to NA were similar. Analysis of the concentration-response relationships demonstrated that the dystrophic ischiatic artery was less sensitive to 5-HT than was the normal artery, although the sensitivity to NA was similar in both vessels. The results of this study are not consistent with the view that muscle fibre necrosis in avian dystrophy is a consequence of muscle anoxia. These data do demonstrate pharmacological differences between dystrophic avian arteries and arteries from normal chickens, but their presence may represent merely the expression of dystrophy in vascular smooth muscle.

Sex differences in the phenotypic expression of avian dystrophy.

Although the gene for muscular dystrophy in chickens is not sex-linked, results from clinical tests suggest that it is expressed differently in males and females. As measurement of muscle contractile responses provides a quantitative index for the severity of the disease, the contractile properties of the extensor digitorum communis muscle were examined in normal and dystrophic chickens with respect to sex. Furthermore, these differences were examined in young (6 to 9 weeks) and old (greater than 6 months) chickens. Results showed that age-related sex differences were apparent for those mechanical parameters of the muscle (in particular the posttetanic potentiation and posttetanic contracture) known to distinguish normal and dystrophic birds. The sex differences observed in the younger group indicate that the female birds were more severely affected by the disease than were the male. In the older group, the male were affected by the disease more severely than age-matched female birds. If the inheritance pattern is truly autosomal then it is likely that one or more developmental factors interact with the dystrophic genotype and alter the dystrophic phenotype.

Miniature end plate potentials recorded from mammalian myoneural junction in vivo.

Fibers of the cat soleus muscle had a mean resting potential of 87 millivolts as measured with an intracellular microelectrode. Miniature end plate potentials had a mean amplitude of 0.95 millivolt, a mean frequency of 1.01 per second, a mean duration of 4.44 milliseconds, and a mean rate of rise of 0.99 volt per second. Two populations of response could be discerned on the basis of rate of rise. Neither alpha-chloralose nor nerve section had any significant effect on the response pattern. The in vivo preparation appears to provide a superior representation of the physiology of the myoneural junction.