In cholinergic neurons, acetylcholine is synthesized from choline and acetyl-coenzyme A (acetyl-CoA). Vesicular acetylcholine transporter (VAChT) transports acetylcholine from the cytoplasm to the lumen of synaptic vesicles where following depolarization, acetylcholine is released in the synaptic cleft and activates muscarinic and nicotinic receptors located on postsynaptic membranes1-3. Acetylcholine released in the synaptic cleft is rapidly hydrolyzed into choline and acetate. Since choline is not de novo synthesized and thereby only made available through diet uptake, choline is recycled back into the cells in order to regenerate acetylcholine.nVAChT is a member of the SLC18 family of transporters. It has 12 membrane spanning domains, with extracellular N- and C-terminal tails. The transporter exchanges cytoplasmic acetylcholine for two vesicular protons.nVAChT is a selective marker of cholinergic neurons and could be used therefore to determine the loss of cholinergic neurons in Alzheimer’s or Alzheimer’s related disease. VAChT knockout mice die after birth. They display a lack of stimulated release of acetylcholine and an underdeveloped neuromuscular junction.
