The Nicotinic Cholinergic Receptors (13)
To read the first article in this series, click here.
To read the previous article in this series, click here.
To watch my accompanying YouTube video to this blog post, click here.
ASSORTMENTS OF SEVENTEEN GENES
There are seventeen nAChR subunits, categorized genetically as α, β, δ, γ, ε. The δ, γ, and ε are only found in muscles, and therefore not relevant to our present review. The neuronal α and β are found on the nicotinic cholinergic receptors in groups of five (called pentameric stoichiometry). Each receptor has an assortment of five genes from CHRNA2-CHRNA9 and CHRNB2-CHRNB4, where the letter A corresponds to an α receptor and the letter B corresponds to a β receptor. CHRNB2, for example, codes for the β2 receptor.
HOMOMERIC AND HETEROMERIC ASSORTMENTS
Neuronal nAChRs form in two ways, either as homomeric receptors, in which all five subunits are the same (eg. α75 and α95), or in heteromeric receptors, in which the five subunits are formed by different α and β subunits. The most common classes of receptors in mammalian brains are α32β43 and α75, where the first receptor has two α3 genes and three β4 genes and the second receptor has five α7 genes. Nicotine has the highest affinity for the α4β2 receptors. In Alzheimer’s disease, 30-50% of the loss in subunits is attributable to losses in α4s, while the α4β2 groups that nicotine has a particularly high affinity for are also greatly diminished as a class.
As mentioned in our discussion on the cholinergic system’s role in depression, the nicotinic cholinergic receptors exhibit paradoxical upregulation in the presence of the agonist nicotine. They do this nonuniformly. In the brain, the medulla oblongata, parts of the cortex, and the hippocampus appear resistant to observed upregulation of receptors, while muscle receptors do not upregulate at all. The 𝛼4𝛽2, 𝛼3, and 𝛼7 upregulate, while 𝛼4𝛽2𝛼5 and 𝛼6 do not upregulate. In general, in the presence of 𝛽3 genes, downregulation is inhibited.
To return to an overview of the blog series on the cholinergic system, click here.
 Wonnacott, S. (1990). The paradox of nicotinic acetylcholine receptor upregulation by nicotine. Trends in pharmacological sciences, 11(6), 216-219.  Warpman, U., & Nordberg, A. (1995). Epibatidine and ABT 418 reveal selective losses of α4β2 nicotinic receptors in Alzheimer brains. Neuroreport: An International Journal for the Rapid Communication of Research in Neuroscience.  Melroy‐Greif, W. E., Stitzel, J. A., & Ehringer, M. A. (2016). Nicotinic acetylcholine receptors: upregulation, age‐related effects and associations with drug use. Genes, Brain and Behavior, 15(1), 89-107.