Restoration of dysgenic muscle contraction and calcium channel function by co-culture with normal spinal cord neurons.
Muscular dysgenesis (mdg) is a spontaneous recessive lethal mutation in the mouse. The disease is characterized by a total lack of excitation-contraction coupling in embryonic skeletal muscle. This developmental abnormality is associated with a drastic deficiency in the expression of voltage-sensitive Ca2+ channels in skeletal muscle without alteration of the properties of voltage-sensitive Na+ channels or of voltage-sensitive Ca2+ channels in cardiac and neuronal cells. Membrane couplings between sarcoplasmic reticulum and the transverse tubules, known as triads, were also found to be drastically altered in embryonic muscle of the homozygous mutant (mdg/mdg). Triads in the mdg/mdg muscle were less numerous, disorganized and lacked spaced densities. This paper shows that co-culture of mdg/mdg myotubes with normal spinal cord neurons re-establishes Ca2+ channel activity, contraction and normal triad organization. The decrease thus cannot be due to a mutation of the Ca2+ channel as previously suggested. Normal nerve cells may supply an essential factor to mutant muscle cells.
D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D005071:Evoked Potentials; D005804:Genes, Lethal; D005808:Genes, Recessive; D007473:Ion Channels / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009119:Muscle Contraction; D009132:Muscles / Q000503:physiopathology*; D009135:Muscular Diseases / Q000235:genetics / Q000503:physiopathology*; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*
D007473:Ion Channels