Development and Regulation of Acetylcholine Receptor Function

Abstract

Nicotinic acetylcholine (ACh) receptors are among the first proteins to be expressed on the membranes of newly differentiated muscle cells. During development, the functional properties of the receptors and their associated channels undergo major changes in many skeletal muscles (Schuetze and Role, 1987). The kind of changes as well as the timetable of the changes depends on the type of muscle being studied (Schuetze, 1980; Kullberg and Owens, 1986). Changes in receptor expression also occur in adult skeletal muscle following denervation (Neher and Sakmann, 1976) and during subsequent reinnervation (Brenner and Sakmann, 1983). Studies on adult muscle have led to the proposition that the development of receptor function depends on the proximity of the receptor to the site of nerve-muscle contact (Cull-Candy et al., 1982; Brenner and Sakmann, 1983). The mechanisms which underlie the regulation of receptor function in developing and adult muscle have been the subject of a large number of studies. In this paper we summarize the results of our studies on the development of ACh receptor function in amphibian muscle and include, as well, the results of complementary studies on both innervated and denervated adult mammalian muscle. We address the issues related to neural regulation of ACh receptor properties by comparing properties of synaptic and nonsynaptic receptors in developing and adult muscle. The possible underlying molecular mechanisms and functional significance of our observations are discussed.