Functional characterization of the human high-affinity choline transporter
1Department of Neurochemistry, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan. okuda@m.u-tokyo.ac.jp
Abstract:
Na(+)-dependent, high-affinity choline uptake in cholinergic neurons is the rate-limiting step in acetylcholine synthesis. Here we report the molecular cloning and functional characterization of the human high-affinity choline transporter (hCHT1). The hCHT1 exhibits significant homology with known members of the Na(+)-dependent glucose transporter family, but not with members of the neurotransmitter transporter family. The human CHT1 gene is 25 kb in length with 9 exons and was assigned to chromosome II at position IIq11-12. Northern blot analysis showed that a 5.4 kb hCHT1 transcript was expressed exclusively in tissues containing cholinergic neurons. When expressed in Xenopus oocytes, the human clone induced Na(+)- and Cl(-)-dependent, high-affinity choline uptake, which was sensitive to the specific inhibitor hemicholinium-3, with a K(i) of 1.3 nM. The hCHT1-mediated choline uptake increased with increasing concentrations of choline, Na(+) and Cl(-), with EC(50) values of 2.0 microM, 76 mM, and 48 mM, and with apparent Hill coefficients of 1, 2.5 and 2.3, respectively.
More Related Videos
09:06Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells
Published on: December 19, 2025
07:47A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters
Published on: April 20, 2015
Related Concept Videos
Cholinergic Neurons: Neurotransmission
Direct-Acting Cholinergic Agonists: Pharmacokinetics
The Significance of Membrane Transport
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
The direct-acting...
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion, mediated...
