The high affinity, hemicholinium-3-sensitive, choline transporter (CHT) is expressed mainly in cholinergic neurones on nerve cell terminals and synaptic vesicles (keratinocytes being an additional location). In autonomic neurones, expression of CHT requires an activity-dependent retrograde signal from postsynaptic neurones [5]. Through recapture of choline generated by the hydrolysis of ACh by acetylcholinesterase, CHT serves to maintain acetylcholine synthesis within the presynaptic terminal [3]. Homozygous mice engineered to lack CHT die within one hour of birth as a result of hypoxia arising from failure of transmission at the neuromuscular junction of the skeletal muscles that support respiration [2]. A low affinity choline uptake mechanism that remains to be identified at the molecular level may involve multiple transporters. In addition, a family of choline transporter-like (CTL) proteins, (which are members of the SLC44 family) with weak Na⁺ dependence have been described [8].

K_i and K_D values for hemicholinium-3 listed in the table are for human CHT expressed in Xenopus laevis oocytes [6], or COS-7 cells [1]. Hemicholinium mustard is a substrate for CHT that causes covalent modification and irreversible inactivation of the transporter. Several exogenous substances (e.g. triethylcholine) that are substrates for CHT act as precursors to cholinergic false transmitters.

1. Apparsundaram S, Ferguson SM, George AL, Blakely RD. (2000) Molecular cloning of a human, hemicholinium-3-sensitive choline transporter. Biochem. Biophys. Res. Commun., 276 (3): 862-7. [PMID:11027560]

2. Ferguson SM, Bazalakova M, Savchenko V, Tapia JC, Wright J, Blakely RD. (2004) Lethal impairment of cholinergic neurotransmission in hemicholinium-3-sensitive choline transporter knockout mice. Proc. Natl. Acad. Sci. U.S.A., 101 (23): 8762-7. [PMID:15173594]

3. Ferguson SM, Blakely RD. (2004) The choline transporter resurfaces: new roles for synaptic vesicles?. Mol. Interv., 4 (1): 22-37. [PMID:14993474]

4. Iwamoto H, Blakely RD, De Felice LJ. (2006) Na+, Cl-, and pH dependence of the human choline transporter (hCHT) in Xenopus oocytes: the proton inactivation hypothesis of hCHT in synaptic vesicles. J. Neurosci., 26 (39): 9851-9. [PMID:17005849]

5. Krishnaswamy A, Cooper E. (2009) An activity-dependent retrograde signal induces the expression of the high-affinity choline transporter in cholinergic neurons. Neuron, 61 (2): 272-86. [PMID:19186169]

6. Okuda T, Haga T. (2000) Functional characterization of the human high-affinity choline transporter. FEBS Lett., 484 (2): 92-7. [PMID:11068039]

7. Okuda T, Haga T. (2003) High-affinity choline transporter. Neurochem. Res., 28 (3-4): 483-8. [PMID:12675135]

8. Traiffort E, Ruat M, O'Regan S, Meunier FM. (2005) Molecular characterization of the family of choline transporter-like proteins and their splice variants. J. Neurochem., 92 (5): 1116-25. [PMID:15715662]