Abstract
Neuronal nicotinic acetylcholine receptors (nAChRs) are abundantly expressed in the central nervous system. Neurons in several brain regions co-express alpha5, alpha4 and beta2 subunits. Changes in the receptor composition and stoichiometry of alpha4 and beta2 containing nAChRs are pertinent to disease states. Several genome-wide association and candidate gene studies have identified polymorphisms in the gene for the alpha5 subunit that are linked to an increased risk for nicotine addiction, alcohol addiction and lung cancer. However more information is required about the functional effects of incorporating a normal or mutated alpha5 subunit into the alpha4beta2 receptor pentamer. Here we examine differences in I-V relationships and dose-response relations between alpha4beta2 receptors and alpha4beta2 receptors including alpha5 subunits containing various mutations to the M2 domain expressed in Xenopus oocytes.
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