In cholinergic neurons, acetylcholine is synthesized from choline and acetyl-coenzyme A (acetyl-CoA). Following depolarization, acetylcholine is released to the synaptic cleft via synaptic vesicles and activates muscarinic and nicotinic receptors located on postsynaptic membranes^1,2. Acetylcholine is then rapidly hydrolyzed into choline and acetate. Since choline is not synthesized de novo and thereby only made available through diet, choline is recycled back into the cells in order to regenerate acetylcholine. For this purpose, choline is taken up by the high affinity choline transporter (CHT)^1,2.

CHT has thirteen transmembrane domains, an extracellular N-terminus and an intracellular C-terminus^3,4. CHT belongs to the Na⁺-dependent glucose transporter family (SLC5). The activity of the transporter can be confirmed by its sensitivity to hemicholimium-3 (HC-3) which inhibits the transport of choline with a K_i of 10-100 nM¹. The activity of CHT reflects that of neurons^1,5 i.e. increased CHT activity indicates an increase in neuronal activity. The increase in the activity of the transporter is due to the increase in the number of transporters and not due to the increase in activity per se. In addition CHT activity is also regulated by second messengers. Phosphorylation of the transporter also seems to determine the activity as it has many consensus phosphorylation sites present in the C-terminal^1,2.

Expression studies reveal that CHT is expressed solely in cholinergic neurons making the transporter a useful marker for detecting these types of neurons⁶.