Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

Stephanie C. Gantz, Brooks G. Robinson, David C. Buck, James R. Bunzow, Rachael L. Neve, John Williams, Kim Neve

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calciumdependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors.

Original languageEnglish (US)
Article numbere09358
JournaleLife
Volume4
Issue numberAUGUST2015
DOIs
StatePublished - Aug 26 2015

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Autoreceptors
Calcium Signaling
Dopamine
Calcium
Protein Isoforms
Dopaminergic Neurons
Cocaine
Neurons
Plasticity
Dopamine D2 Receptors
G-Protein-Coupled Receptors
Mesencephalon
GTP-Binding Proteins
Knockout Mice
Substance-Related Disorders
Brain
Potassium
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Gantz, S. C., Robinson, B. G., Buck, D. C., Bunzow, J. R., Neve, R. L., Williams, J., & Neve, K. (2015). Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium. eLife, 4(AUGUST2015), [e09358]. https://doi.org/10.7554/eLife.09358

Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium. / Gantz, Stephanie C.; Robinson, Brooks G.; Buck, David C.; Bunzow, James R.; Neve, Rachael L.; Williams, John; Neve, Kim.

In: eLife, Vol. 4, No. AUGUST2015, e09358, 26.08.2015.

Research output: Contribution to journalArticle

Gantz, SC, Robinson, BG, Buck, DC, Bunzow, JR, Neve, RL, Williams, J & Neve, K 2015, 'Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium', eLife, vol. 4, no. AUGUST2015, e09358. https://doi.org/10.7554/eLife.09358
Gantz SC, Robinson BG, Buck DC, Bunzow JR, Neve RL, Williams J et al. Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium. eLife. 2015 Aug 26;4(AUGUST2015). e09358. https://doi.org/10.7554/eLife.09358
Gantz, Stephanie C. ; Robinson, Brooks G. ; Buck, David C. ; Bunzow, James R. ; Neve, Rachael L. ; Williams, John ; Neve, Kim. / Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium. In: eLife. 2015 ; Vol. 4, No. AUGUST2015.
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