FUNCTIONAL CONTRIBUTION OF NEURONAL ACHR SUBUNITS REVEALED BY ANTISENSE OLIGONUCLEOTIDES

Although multiple related genes encoding nicotinic acetylcholine receptor (AChR) subunits have been identified, how each of these subunits contributes to AChRs in neurons is not known. Sympathetic neurons express four classes of AChR channels and six AChR subunit genes (alpha-3, alpha-4, alpha-5, alpha-7, beta-2, and beta-4). The contribution of individual subunits to AChR channel subtypes in these neurons was examined by selective deletion with antisense oligonucleotides. An alpha-3 antisense oligonucleotide decreased the number and altered the properties of the normally expressed ACh-activated channels. The remaining AChR channels have distinct biophysical and pharmacological properties that indicate an important functional contribution of the alpha-7 subunit.