Activity-dependent regulation of the dopamine transporter is mediated by Ca2+/calmodulin-dependent protein kinase signaling

Shalini Padmanabhan, Nevin A Lambert, Balakrishna M. Prasad

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The mechanisms regulating expression of the dopamine transporter are poorly understood. We tested the hypothesis that neuronal activity is one of the non-genetic determinants of dopamine transporter abundance. Sustained changes in neuronal activity caused by tetrodotoxin and 4-aminopyridine altered the dopamine uptake and abundance of dopamine transporter and its mRNA in rat mesencephalic cultures. The altered neuronal activity caused by these two drugs is accompanied by changes in intracellular calcium concentrations and Ca 2+/calmodulin-dependent protein (CaM) kinase II activity in dopamine neurons. Chronic treatment with an L-type calcium channel blocker (nifedipine) or CaM kinase inhibitor (KN93) decreased dopamine transporter-mediated uptake and occluded the effects of tetrodotoxin and 4-aminopyridine. These data suggest that neuronal activity can regulate dopamine transporter function and abundance via calcium/CaM kinase II signaling.

Original languageEnglish (US)
Pages (from-to)2017-2027
Number of pages11
JournalEuropean Journal of Neuroscience
Volume28
Issue number10
DOIs
StatePublished - Nov 1 2008

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinases
Dopamine Plasma Membrane Transport Proteins
Calcium-Calmodulin-Dependent Protein Kinase Type 2
4-Aminopyridine
Tetrodotoxin
Calcium
L-Type Calcium Channels
Dopaminergic Neurons
Calcium Channel Blockers
Nifedipine
Dopamine
Phosphotransferases
Messenger RNA
Pharmaceutical Preparations

Keywords

  • Action potential
  • Calcium
  • Mesencephalic
  • Monoamine
  • Rat
  • Uptake

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activity-dependent regulation of the dopamine transporter is mediated by Ca2+/calmodulin-dependent protein kinase signaling. / Padmanabhan, Shalini; Lambert, Nevin A; Prasad, Balakrishna M.

In: European Journal of Neuroscience, Vol. 28, No. 10, 01.11.2008, p. 2017-2027.

Research output: Contribution to journalArticle

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