Changes in genotypic expression, development, and the effects of chronic penicillamine treatment on the electrical properties of the posterior latissimus dorsi muscle in two lines of normal and dystrophic chickens

Abstract When line 304 dystrophic chickens were outcrossed, a new line of genetically dystrophic chickens designated 413 was produced together with a genetically related normal animal (line 412). The expected alteration in membrane resistance in the surface fibers of the posterior latissimus dorsi (PLD) muscle was eliminated in this new line of dystrophic chickens. Although the input resistance of PLD fibers from both lines 200 and 304 chickens declined simultaneously from 1 to 2 Mω at 5 weeks ex ovo to 0.3 Mω at 17 to 33 weeks ex ovo , specific membrane resistance, membrane space and time constants, and fiber radius of line 304-dystrophic fibers were significantly greater than in line 200-normal fibers at various times ex ovo . Only the membrane time constant and capacitance of PLD fibers of line 413-dystrophic chickens were greater than in line 412-normal at 8 weeks ex ovo . Other differences in electrical properties were also seen. Only in line 413-dystrophic chickens were the resting membrane potentials and action potential properties significantly different from line 412. Outcrossing of line 304 chickens [has thus] revealed that various electrical properties of muscle such as membrane resistance are under genetic control but did not influence the development of dystrophy. On the other hand, alterations in action potential activity persists after outcrossing and appear to have a greater role in the symptomatology of muscular dystrophy. A therapeutic approach to the disease using oral d -penicillamine treatment was initiated 9 days ex ovo in normal (line 412) and dystrophic (line 413) chickens of either sex and continued 7 to 10 weeks. An improvement in the righting ability of treated vs. untreated dystrophic birds was first noted at 6 weeks ex ovo , and by 8 weeks, treated dystrophic chickens were always able to right themselves whereas untreated dystrophic chickens failed 75% of the time. The body weights and rates of growth in untreated normal and dystrophic chickens were similar but that of treated birds were 35 to 40% lower. The drug had no effect on the resting membrane potential of PLD surface fibers in treated chickens. The beneficial effect of the drug was initially correlated with the ability of the PLD muscle to respond with a twitch to single indirect stimulation and to the absence of a decrementing response in muscle to repetitive nerve stimulation. Penicillamine only decreased the action potential threshold in dystrophic chickens. Penicillamine treatment reduced the depression of the probability of release of transmitter in dystrophic muscle. The higher threshold for excitation and greater resting membrane potential in the newer line of dystrophic chickens may account in part for the inability of these chickens to right themselves when placed on their backs. It is suggested that the beneficial effect of penicillamine is related to an alteration of synaptic function and lowering of the threshold for excitation in muscle.