Neurons can maintain multiple classes of nicotinic acetylcholine receptors distinguished by different subunit compositions

Abstract

Although 10 genes have been cloned encoding putative subunits of neuronal nicotinic acetylcholine receptors, little is known about the variety or subunit composition of such receptors expressed by individual neurons. Chick ciliary ganglion neurons express five of the known genes and assemble a class of synaptic-type receptors collectively containing gene products from three of them: alpha 3, beta 4, and alpha 5. Using subunit-specific monoclonal antibodies, we show here that all of the synaptic-type acetylcholine receptors having alpha 3 also have beta 4 subunits and vice versa. In addition, most, if not all, of the alpha 5 gene product present in fully assembled receptors is associated with both alpha 3 and beta 4 subunits. Although the receptors may be homogeneous in these respects, only about 20% of them also contain the fourth gene product, beta 2, newly identified in the ganglion; essentially all of the neurons express the beta 2 gene. No beta 2 subunits are found coassembled with the fifth acetylcholine receptor gene product expressed by the neurons, alpha 7, which has been shown previously to comprise a class of abundant, nonsynaptic receptors on the cells. The identification of three acetylcholine receptor subtypes distinguished by subunit composition on the same neurons provokes questions about their individual physiological roles.