Further observations on the distribution of acetylcholine‐reactive sites in skeletal muscle

It has been known since Langley's (1907) work that the sensitivity of a muscle to certain chemical stimuli shows striking differences along the fibre surface, the region of the neuromuscular junction being much more reactive than the rest of the fibre. Recently it has been found that marked changes can be produced in this distribution of chemoreceptive properties, for example, by complete or partial denervation and re-innervation of the muscle fibre (Ginetzinsky & Shamarina, 1942; Axelsson & Thesleff, 1959; Miledi, 1960a, c; Diamond & Miledi, 1962), and by direct muscle transection (Katz & Miledi, 1961 b). While extending this work we came across several additional observations. One is the degree of variability to be found among apparently normal muscle fibres: although the sensitivity to acetylcholine (ACh) at the myoneural junction is much higher than elsewhere, the low level to which the sensitivity falls in the extra-junctional region varies in different fibres over more than a thousandfold range, between less than 1/500,000 and approximately 1/100 of the maximum at the end-plate. Another observation was that the muscle-tendon junction often shows a separate peak of ACh sensitivity, much lower than that at the end-plate, but well above that of the rest of the fibre. This is of interest because of the local concentration of ACh-esterase which has been reported at myoneural and muscle-tendon junctions by Couteaux (1953), Gerebtzoff (1954) and Schwarzacher (1960b).