Heteromeric α7β2 Nicotinic Acetylcholine Receptors in the Brain

The alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR) is highly expressed in the brain, where it maintains various neuronal functions including (but not limited to) learning and memory. In addition, the protein expression levels of alpha 7 nAChRs are altered in various brain disorders. The classic rule governing alpha 7 nAChR assembly in the mammalian brain was that it was assembled from five alpha 7 subunits to form a homomeric receptor pentamer. However, emerging evidence demonstrates the presence of heteromeric alpha 7 nAChRs in heterologously expressed systems and naturally in brain neurons, where alpha 7 subunits are co-assembled with beta 2 subunits to form a novel type of alpha 7 beta 2 nAChR. Interestingly, the alpha 7 beta 2 nAChR exhibits distinctive function and pharmacology from traditional homomeric alpha 7 nAChRs. We review recent advances in probing the distribution, function, pharmacology, pathophysiology, and stoichiometry of the heteromeric alpha 7 beta 2 nAChR, which have provided, new insights into the understanding of a novel target of cholinergic signaling.