Restoration of dysgenic muscle contraction and calcium channel function by co-culture with normal spinal cord neurons

Abstract

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^1–4. This developmental abnormality is associated with a drastic deficiency in the expression of voltage-sensitive Ca²⁺ channels in skeletal muscle^3–5 without alteration of the properties of voltage-sensitive Na⁺ channels⁴ or of voltage-sensitive Ca²⁺ channels in cardiac^3,5 and neuronal cells⁵. 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^3,6. 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 suggested⁵. Normal nerve cells may supply an essential factor to mutant muscle cells.