An electrophysiological study of skeletal muscle fibres in the 'muscular dysgenesis' mutation of the mouse.

Experiments were performed on muscles of 18-19 day mice fetuses affected with muscular dysgenesis (mdg). Action potentials generated by electrical stimulation or potassium depolarization failed to trigger muscle contraction in mdg muscle fibres. By contrast, muscle contraction could be obtained by caffeine (15 mM) and, to a lesser degree, by nerve stimulation. We conclude that a defect in excitation-contraction (E-C) coupling is the cause of muscle paralysis. An early after potential (EAP) was present in the decay phase of the action potential and a potential 'creep' occurred in response to hyperpolarizing current pulses which can be taken as evidence for the presence of T-tubules in mdg muscle fibres. Data obtained from square pulse analysis and EAP measurements indicate larger input impedance and membrane time constant in mdg as compared to controls, which contrasts with similar surface membrane time constant (as estimated from the foot of the action potential) in both types of muscle. The excitability of the T-tubule system was tested by recording action potentials at early stages of TTX (5 X 10(-7) M) perfusion or washout in mdg and control muscles. In both cases, the action potentials decreased in amplitude and rate of rise and displayed two peaks, the second of which was suppressed by detubulation using the formamide treatment. This indicates action potential generation in the T-tubule membrane of mdg muscles. In all the impaled muscle fibers, nerve stimulation evoked epps which were accompanied by a weak local contraction in relation with Ca2+ influx through postsynaptic channels.(ABSTRACT TRUNCATED AT 250 WORDS)