Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor Journal Article


Author(s): Vyleta, Nicholas P; Smith, Stephen M
Article Title: Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor
Affiliation IST Austria
Abstract: Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release.
Journal Title: European Journal of Neuroscience
Volume: 31
Issue 12
ISSN: 1460-9568
Publisher: Wiley  
Date Published: 2011-03-01
Start Page: 4593
End Page: 4606
URL:
DOI: 10.1523/JNEUROSCI.6398-10.2011
Open access: yes (repository)