Ultrastructural demonstration and analytical application of extrajunctional receptors of denervated human and rat skeletal muscle fibres

WE describe a new approach for distinguishing denervated from normal skeletal muscle fibres, based on the visualisation of differences in distribution of acetylcholine (ACh) receptors in the sarcolemma. Iontophoretic application of ACh^1,2 and autoradiography with labelled α-bungarotoxin (αBuTX)^3,4 have shown that after denervation (and before innervation⁵) ACh receptors appear throughout the sarcolemmal membrane, in contrast to their normal location in the neuromuscular junction. Using an immunopeiroxidase staining technique ^6,7 to localise αBuTX, which binds specifically to ACh receptors^3,4,8, we now have a rapid and convenient method for high resolution, at light and electron microscopic levels, of the ACh receptors present throughout the sarcolemmal membrane of defectively innervated human and rat skeletal muscle fibres. We have used this immunoperoxidase method of molecular probing to analyse muscle biopsies in various human neuromuscular diseases and animal models.