Proton Inactivation Of Choline Transporters

Hideki Iwamoto, Randy D. Blakely, and Louis J. De Felice

Choline transporters (CHTs) are concentrated at cholinergic nerve terminals at which these sodium-coupled transport molecules deliver the goods to the cytoplasm for subsequent acetylcholine (ACh) synthesis. Iwamoto et al. examined the biophysical properties of the human CHT expressed in Xenopus laevis oocytes. Several interesting properties emerged, including constitutive leakage current in the absence of substrate and variable stoichiometry of electrogenic transport. Their results may also solve a long-standing puzzle. Because CHTs can also transport ACh at high concentrations, and the transporters are highly expressed on presynaptic vesicles, transmitter could leak from ACh-containing synaptic vesicles. However, choline transport and current were inactivated at low pH. The authors hypothesize that the acidic pH in synaptic vesicles inactivates CHTs. However, once CHT-containing vesicles fuse with the plasma membrane, the neutral extracellular pH re-activates the transporter. It seems that CHTs come with a built-in ON-OFF switch.

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Proton Inactivation Of Choline Transporters