N-methyl-4-phenylpyridinium (MPP+) selectively destroys dopaminergic neurons and induces the symptoms of Parkinson’s in humans and other primates. Although selective dopaminergic toxicity of MPP+ has been primarily attributed to the specific uptake through dopamine transporter (DAT), recent studies show that MPP+ is taken up not only into dopaminergic cells, but also into most other cells through multiple pathways. Here we show that a previously unidentified Na+/Cl--independent,Ca2+-sensitive MPP+ uptake pathway is present specifically in dopaminergic cells butnot in other cell types. We further show that both DA and Ca2+ are also substrates for this pathway suggesting that it is a novel non-specific cation transporter. We propose that the specific dopaminergic toxicity of MPP+ could be a consequence of itsinterference with the physiological function(s) of this transporter anda better understanding of its physiological role may provide clues to the etiology of sporadic PD.

Novel Na+-independent Ca2+/dopamine/ MPP+uptake system is present in dopaminergic cells

251st National Meeting (2016)

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