A comparative study of contractile responses in diaphragm muscles of normal and dystrophic (C57BL/6J dy2J/dy2J) mice.

Potassium and caffeine contractures of isolated small bundles (100 to 200 micron diameter) of muscle fibers isolated from the diaphragm of normal and dystrophic (C57BL/6J dy2J/dy2J) mice were compared. In diaphragms of pathologic mice (3 to 5 months old) the resting potential, the characteristics of the twitch, and some histological examinations were typical of dystrophic muscles. The slopes of the relationships between the steady membrane potential and log [K]0 were similar for the two types of cells. In 110 mM and 146 mM K there were no significant differences in the time course of the contractures and reduction in [Ca]0 decreased the time to peak and the time constant of relaxation to the same extent; the relative efficiency of [Mg]0 compared with [Ca]0 was equivalent. Repriming of K contractures at different external calcium concentrations indicated that the normal diaphragm did not have any special advantage. The exposure of isolated strips to a solution containing caffeine resulted in a similar increase of the strength of the regularly evoked twitch responses. However, the contractures elicited by 1.25 to 20 mM caffeine showed a subsensitivity of the dystrophic diaphragm (KmDys = 9.3 KmN) and the rate of relaxation was significantly slower than in normal muscle (in 20 mM caffeine, 50% decay time for normal muscle was 25.2 +/- 7.6 s and for dystrophic muscle 54.8 +/- 11.2 s. These results suggest an absence of major alterations in the mechanism of excitation-contraction coupling associated with dystrophy, except for a change in the specific element of the sarcoplasmic reticulum where caffeine acts.