This critical function is accomplished by the secondary active transport of neurotransmitters against their concentration gradient into synaptic vesicles

As proton exchangers, VMATs rely on the proton gradient generated by the V-type ATPase across the vesicular membrane and the import of chloride via the ClC-3 chloride channels.

Data from many labs have demonstrated that proper packaging of dopamine into vesicles is critical since cytosolic dopamine is neurotoxic.

In vitro experiments suggest that the relative vulnerability of dopamine neurons in PD may be mediated by cytosolic dopamine

Furthermore, mice that express DAT on non-dopaminergic striatal neurons, which lack VMAT2, take up dopamine into those neurons, but do not store it in vesicles, producing motor deficits and profound striatal neurodegeneration, accompanied by markers of increased dopamine oxidation