The molecular biology of neuronal nicotinic acetylcholine receptors.

The molecular cloning of genes encoding neuronal nicotinic acetylcholine receptors (nAChRs) has made possible a better understanding of the pharmacology and toxicology of cholinergic compounds. Neuronal nAChRs are related in structure to the nAChRs present at the neuromuscular junction. They are composed of multiple subunits designated either alpha and beta. Eight alpha and three beta subunit genes have been cloned. The alpha subunits contain the ligand binding sites, whereas beta subunits are structural subunits that contribute to the function of the receptor. A large number of nAChRs can be formed from different combinations of alpha and beta subunits. Different combinations of alpha and beta subunits can produce receptors in vitro with distinct ion conducting properties. Each subunit gene is expressed in a distinct pattern in the nervous system. The expression of at least some of the nAChR subunit genes is regulated during development and by cell-cell interactions. Each neuronal nAChR subtype has a distinct pharmacology. Both alpha and beta subunits contribute to the pharmacological properties of each subtype. The expression of multiple nAChR subtypes may allow for precise control of neurotransmission mediated by acetylcholine in diverse populations of neurons.