Excitation-contraction uncoupling in the developing skeletal muscle of the muscular dysgenesis mouse embryo.
The muscular dysgenesis recessive autosomal mutation is characterized by a total lack of muscular contraction and a myofibrillar non-organization. Many abnormalities involved in the excitation-contraction coupling are found in mdg/mdg myotubes: 1) the internal structural organization of the membrane coupling between the sarcoplasmic reticulum (SR) and the transverse (T)-tubule forming the triadic association is defective: the triad number is decreased in the muscle and there are a lack of periodic densities between the SR and T-tubule apposed membranes. 2) the voltage-dependent Ca2+ channel contents, identified by binding with the specific blocker PN 200-110, are decreased. The two fast (30 ms) and slow (100 ms) Ca2+ currents present in normal myotubes are absent in mdg/mdg myotubes in vitro. 3) the Ca2+-dependent K+ conductance triggering an action potential followed by a long lasting after hyperpolarization (ahp) is absent in mdg/mdg myotubes. This indicates a lack of the free intracellular Ca2+ increased by the action potential. These results suggest that: 1) the lack of differentiated triadic junctions is directly correlated with very low amounts of voltage-dependent Ca2+ channels; 2) the low amount of Ca2+ channels results directly in decreased Ca2+ currents; 3) the decreased Ca2+ currents are the consequence of the low intracellular Ca2+ concentration which is not sufficient to trigger a contraction. However, the addition of normal motoneurones to mdg/mdg myotubes in culture induces, few days later, an increase in Ca2+ currents.
D000818:Animals; D051379:Mice; D009132:Muscles / Q000002:abnormalities* / Q000196:embryology / Q000503:physiopathology