QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 20, 2009, 29(20):6568-6579; doi:10.1523/JNEUROSCI.0181-09.2009

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Patel, J. C. Articles by Rice, M. E. PubMed PubMed Citation Articles by Patel, J. C. Articles by Rice, M. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CADMIUM COMPOUNDS CADMIUM, ELEMENTAL CALCIUM COMPOUNDS CALCIUM, ELEMENTAL

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Mobilization of Calcium from Intracellular Stores Facilitates Somatodendritic Dopamine Release

Jyoti C. Patel,¹ Paul Witkovsky,² Marat V. Avshalumov,¹ and Margaret E. Rice^1,3

Departments of ¹Neurosurgery, ²Ophthalmology, and ³Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016

Correspondence should be addressed to Dr. Margaret E. Rice, Department of Physiology and Neuroscience, New York University School of Medicine, 550 First Avenue, New York, NY 10016. Email: margaret.rice{at}nyu.edu

Somatodendritic dopamine (DA) release in the substantia nigra pars compacta (SNc) shows a limited dependence on extracellular calcium concentration ([Ca²⁺]_o), suggesting the involvement of intracellular Ca²⁺ stores. Here, using immunocytochemistry we demonstrate the presence of the sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2) that sequesters cytosolic Ca²⁺ into the endoplasmic reticulum (ER), as well as inositol 1,4,5-triphosphate receptors (IP₃Rs) and ryanodine receptors (RyRs) in DAergic neurons. Notably, RyRs were clustered at the plasma membrane, poised for activation by Ca²⁺ entry. Using fast-scan cyclic voltammetry to monitor evoked extracellular DA concentration ([DA]_o) in midbrain slices, we found that SERCA inhibition by cyclopiazonic acid (CPA) decreased evoked [DA]_o in the SNc, indicating a functional role for ER Ca²⁺ stores in somatodendritic DA release. Implicating IP₃R-dependent stores, an IP₃R antagonist, 2-APB, also decreased evoked [DA]_o. Moreover, DHPG, an agonist of group I metabotropic glutamate receptors (mGluR1s, which couple to IP₃ production), increased somatodendritic DA release, whereas CPCCOEt, an mGluR1 antagonist, suppressed it. Release suppression by mGluR1 blockade was prevented by 2-APB or CPA, indicating facilitation of DA release by endogenous glutamate acting via mGluR1s and IP₃R-gated Ca²⁺ stores. Similarly, activation of RyRs by caffeine increased [Ca²⁺]_i and elevated evoked [DA]_o. The increase in DA release was prevented by a RyR blocker, dantrolene, and by CPA. Importantly, the efficacy of dantrolene was enhanced in low [Ca²⁺]_o, suggesting a mechanism for maintenance of somatodendritic DA release with limited Ca²⁺ entry. Thus, both mGluR1-linked IP₃R- and RyR-dependent ER Ca²⁺ stores facilitate somatodendritic DA release in the SNc.

---

Received Jan. 12, 2009; revised March 17, 2009; accepted March 27, 2009.

Correspondence should be addressed to Dr. Margaret E. Rice, Department of Physiology and Neuroscience, New York University School of Medicine, 550 First Avenue, New York, NY 10016. Email: margaret.rice{at}nyu.edu

This article has been cited by other articles:

				F.-W. Zhou, Y. Jin, S. G. Matta, M. Xu, and F.-M. Zhou An Ultra-Short Dopamine Pathway Regulates Basal Ganglia Output J. Neurosci., August 19, 2009; 29(33): 10424 - 10435. [Abstract] [Full Text] [PDF]

				L. Bao, M. V. Avshalumov, J. C. Patel, C. R. Lee, E. W. Miller, C. J. Chang, and M. E. Rice Mitochondria Are the Source of Hydrogen Peroxide for Dynamic Brain-Cell Signaling J. Neurosci., July 15, 2009; 29(28): 9002 - 9010. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help