P2X₂ 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 P2X₂ 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 P2X₂ receptors is used for ACh synthesis using a recombinant system. When P2X₂ receptors expressed on HEK293 cell lines were stimulated with ATP, intracellular ACh concentrations increased. These results suggest that P2X₂ receptors function in a novel pathway that supplies choline for ACh synthesis.