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Calcium signaling mediates activity‐dependent regulation of the dopamine transporter expression
Author(s) -
Padmanabhan Shalini,
Prasad Balakrishna M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1176-b
Subject(s) - dopamine transporter , camk , chemistry , dopamine , tyrosine hydroxylase , calcium , nifedipine , tetrodotoxin , calmodulin , endocrinology , medicine , extracellular , pharmacology , microbiology and biotechnology , dopaminergic , phosphorylation , protein kinase a , biology , biochemistry , organic chemistry , autophosphorylation
Mechanisms regulating the expression of dopamine transporter (DAT), a primary target for psychostimulant drugs, are not well understood. The objective of this study was to test the role of calcium mediated signaling in activity‐dependent regulation of DAT expression. Chronic perturbations in neuronal activity caused by 5‐day treatment with 4‐aminopyridine (4‐AP), tetrodotoxin (TTX) or KCl altered DAT expression and function in cultured mesencephalic neurons. 4‐AP treatment increased DAT expression while TTX had an opposite effect. Chronic exposure to high extracellular potassium (30mM KCl) caused a decrease in DAT expression implying that phasic changes in membrane potential observed during neuronal firing rather than sustained depolarization are important for maintaining DAT expression. Blockade of L‐type calcium channels with nifedipine or inhibition of Ca 2+ /calmodulin‐dependent protein kinases (CaMK) with KN93 decreased DAT mediated uptake. Nifedipine and KN93 also blocked the increase in DAT mediated uptake caused by 4‐AP and occluded the effects of TTX and KCl on dopamine uptake. Furthermore, activity of CaMK assessed by phosphorylation state of CaMKII and tyrosine hydroxylase was increased by chronic treatment with 4‐AP while chronic exposure to TTX and KCl decreased CaMK activity. Taken together, our data suggest that the calcium‐CaMK pathway mediates activity dependent DAT regulation. This work was supported by funds from the Medical College of Georgia.