Appearance of the slow Ca conductance in myotubes from mutant mice with "muscular dysgenesis"

Abstract

Voltage gated Ca conductance in skeletal muscle cells from mice with muscular dysgenesis (mdg/mdg) and from normal mice was studied using the whole cell recording technique. The physiological properties of the myotubes from the mutant mice (uncoupling of excitation-contraction, deficiency in the voltage gated slow Ca conductance) were changed to normal when the mdg/mdg myotubes were cocultured with spinal cord cells from normal mice. Spinal cord cells from mutant mice failed to induce normal muscle activity in the mutant myotubes. In aged mutant myotubes cultured without spinal cord cells, the slow Ca conductance sometimes developed, although with smaller amplitude. The number of mdg/mdg myotubes with partial development of the slow Ca conductance increased with the age of the culture. E-C coupling was never established in aged mutant myotubes. The phenotypic reversion did not require functional synaptic transmission since it was also obtained when neuromuscular transmission was chronically blocked with alpha-bungarotoxin (4-40 micrograms/ml).