Diversity and patterns of regulation of nicotinic receptor subtypes.

In our studies we explored the functional relevance of nAChR diversity, in part from the perspective of nAChR as ideal targets for regulatory influences, including those mediated via actions of ligands at other "interacting" receptors. We explored possible mechanisms for nAChR regulation and roles played by nAChR subtype and subunit diversity in those processes. We showed that regulatory factors can influence nAChR numbers at transcriptional and posttranscriptional levels and can affect nAChR function and subcellular distribution. We also demonstrated that nAChR expression can be influenced (1) by nicotinic ligands, (2) by second messengers, (3) by growth factors, (4) by agents targeting the nucleus, and (5) by agents targeting the cytoskeleton. We found common effects of some regulatory influences on more than one nAChR subtype, and we found instances where regulatory influences differ for different cell and nAChR types. Even from the very limited number of these initial studies, it is evident that nAChR subunit and subtype diversity, which alone can provide diversity in nAChR functions, localization, and ligand sensitivity, dovetails with diversity in cellular signaling mechanisms that can affect nAChR expression to amplify the potential functional plasticity of cholinoceptive cells. As examples, we discussed potential roles for nAChR diversity and regulatory plasticity in synapse remodeling and in changes in neuronal circuit conditions. These examples illustrate how nAChR diversity could play important roles in the regulation of nervous system function.