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Modulation of Dopamine Transporter Activity by Nicotinic Acetylcholine Receptors and Membrane Depolarization in Rat Pheochromocytoma PC12 Cells
Author(s) -
Huang ChuenLin,
Chen HsiaoChun,
Huang NaiKuei,
Yang DeMing,
Kao LungSen,
Chen JinChung,
Lai HsingLin,
Chern Yijuang
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722437.x
Subject(s) - depolarization , dopamine , neuroscience , chemistry , acetylcholine receptor , nicotinic agonist , acetylcholine , dopamine transporter , microbiology and biotechnology , biophysics , modulation (music) , ganglion type nicotinic receptor , receptor , biology , endocrinology , dopaminergic , nicotinic acetylcholine receptor , biochemistry , physics , acoustics
To elucidate the regulation of the rat dopaminetransporter (rDAT), we established several PC12 variants overexpressing therDAT. Treating these cells with a nicotinic agonist(1,1‐dimethyl‐4‐phenylpiperazinium iodide, 30 μ M ) depolarized theplasma membrane potential from ‐31 ± 2 to 43 ± 5 mV andinhibited rDAT activity significantly in a calcium‐ and protein kinaseC‐independent manner. Membrane depolarization by a high external K + concentration or two K + channel blockers (tetraethylammoniumhydroxide and BaCl 2 ) also resulted in a marked inhibition of rDATactivity. Such inhibition of dopamine uptake is due to a reduction in V max , with no marked effect on the K m for dopamine. The potency of cocaine in inhibiting dopamine uptake was notsignificantly altered, whereas that of amphetamine was slightly enhanced bymembrane depolarization. Removing extracellular Ca 2+ or blocking the voltage‐sensitive L‐type calcium channels using nifedipine did not exert any significant effect on the inhibition of rDAT activity by depolarization. These data confirm that calcium influx on depolarization is not required for inhibition of the rDAT. Collectively, our data suggest that rDAT activity can be altered by a neurotransmitter that modulates the membrane potential, thus suggesting an exquisite mechanism for the fine‐tuning of dopamine levels in the synapse.