Abstract
The neuronal plasma membrane dopamine (DA) transporter (DAT) is essential for the maintenance of DA homeostasis in the brain. Both DAT and a‐synuclein (a‐syn) are expressed in the presynaptic terminals of dopaminergic neurons. a‐syn and DAT form a stable heteromeric complex in co‐transfected cells and mesencephalic neurons (Lee, 2001; Wersinger, 2003). Dysregulation of DA homeostasis is implicated in neurodegenerative diseases, drug addiction and neuropsychiatric disorders. a‐syn is suggested to regulate DA homeostasis, but the mechanism of a‐syn modulation of DAT activity is unknown. We examined how a‐syn affects DAT activity by utilizing dual pipette whole‐cell patch clamp recording, and substrate fluorescence imaging, in immortalized DA neurons and cells stably expressing DAT. Co‐expression of a‐syn and DAT decreased the uptake rate of a fluorescent substrate, ASP+, via DAT. Dialysis of 5 or 10 microM a‐syn via the whole‐cell path pipette stimulated a Na+ independent but Cl‐ sensitive inward current in DAT‐expressing cells. This current is absent when heat inactivated a‐syn is dialyzed into the cells. The a‐syn‐stimulated inward current is eliminated by DAT blockers. Our findings indicate that a‐syn stimulates a DAT‐mediated Cl‐ current. Furthermore, our dual pipette whole‐cell patch method may serve as a model to study the effects of a‐syn on DAT function and DA homeostasis.
Published Version
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