The effects of electrical inactivity and denervation on the distribution of acetylcholine receptors in developing rat muscle

Abstract

Explants of thoracic body wall from rat embryos, including intercostal muscles, ribs, and the adjacent segments of spinal cord, were maintained in organ culture. Nerve-muscle differentiation proceeded in culture with a pattern and time course similar to that of the same synapses developing in utero. To understand further the factors that regulate acetylcholine sensitivity in developing rat myotubes, we studied the effects of electrical inactivity and denervation on the distribution of acetylcholine receptors. When muscle and spinal cord were explanted at 15 days of gestation, prior to the appearance of junctional receptor clusters, intact nerve terminals were required to initiate receptor aggregation at the site of nerve-muscle junction. Electrical activity was not necessary for induction of these primary junctional clusters. Inactivity resulted, however, in the appearance of secondary multiple receptor clusters at random sites along the fibers. In the presence of tetrodotoxin, the electrically inactive nerve terminals sprouted; this was accompanied by the enlargement of the junctional receptor clusters, at the end plate, but there was no correlation between nerve sprouting and the location of extrajunctional receptor aggregates. Later in development, at a time when the junctional receptors are metabolically more stable, terminal sprouting failed to induce the increase in size of junctional receptor aggregates.