| Title | Mobilization of calcium from intracellular stores facilitates somatodendritic dopamine release. | | Author(s) | Patel JC, Witkovsky P, Avshalumov MV, Rice ME | | Institution | Department of Neurosurgery, New York University School of Medicine, New York, New York 10016, USA. | | Source | J Neurosci 2009 May 20; 29(20):6568-79. | | MeSH | Animals
Axons
Boron Compounds
Cadmium
Calcium
Calcium Channels, L-Type
Calcium Signaling
Chelating Agents
Chromones
Dendrites
Dopamine
Egtazic Acid
Electric Stimulation
Electrochemical Techniques
Endoplasmic Reticulum
Enzyme Inhibitors
Guinea Pigs
Indoles
Inositol 1,4,5-Trisphosphate Receptors
Intracellular Fluid
Male
Membrane Potentials
Methoxyhydroxyphenylglycol
Neurons
Patch-Clamp Techniques
Receptors, Metabotropic Glutamate
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Substantia Nigra
Tyrosine 3-Monooxygenase
| | Abstract | Somatodendritic dopamine (DA) release in the substantia nigra pars compacta (SNc) shows a limited dependence on extracellular calcium concentration ([Ca(2+)](o)), suggesting the involvement of intracellular Ca(2+) stores. Here, using immunocytochemistry we demonstrate the presence of the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) that sequesters cytosolic Ca(2+) into the endoplasmic reticulum (ER), as well as inositol 1,4,5-triphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) in DAergic neurons. Notably, RyRs were clustered at the plasma membrane, poised for activation by Ca(2+) 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 Ca(2+) stores in somatodendritic DA release. Implicating IP(3)R-dependent stores, an IP(3)R antagonist, 2-APB, also decreased evoked [DA](o). Moreover, DHPG, an agonist of group I metabotropic glutamate receptors (mGluR1s, which couple to IP(3) 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 IP(3)R-gated Ca(2+) stores. Similarly, activation of RyRs by caffeine increased [Ca(2+)](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 [Ca(2+)](o), suggesting a mechanism for maintenance of somatodendritic DA release with limited Ca(2+) entry. Thus, both mGluR1-linked IP(3)R- and RyR-dependent ER Ca(2+) stores facilitate somatodendritic DA release in the SNc. | | Language | eng | | Pub Type(s) | In Vitro
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19458227 |
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