P2X(2) receptors supply extracellular choline as a substrate for acetylcholine synthesis

Acetylcholine (ACh), an excitatory neurotransmitter, is biosynthesized from choline in cholinergic neurons. Import from the extracellular space to the intracellular environment through the high‐affinity choline transporter is currently regarded to be the only source of choline for ACh synthesis. We recently demonstrated that the P2X(2) receptor, through which large cations permeate, functions as an alternative pathway for choline transport in the mouse retina. In the present study, we investigated whether choline entering cells through P2X(2) receptors is used for ACh synthesis using a recombinant system. When P2X(2) receptors expressed on HEK293 cell lines were stimulated with ATP, intracellular ACh concentrations increased. These results suggest that P2X(2) receptors function in a novel pathway that supplies choline for ACh synthesis.