Role of zinc influx via AMPA/kainate receptor activation in metabotropic glutamate receptor-mediated calcium release
✍ Scribed by Atsushi Takeda; Sayuri Fuke; Akira Minami; Naoto Oku
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 332 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
The uptake of free zinc into CA3 pyramidal cells and its significance was examined in rat hippocampal slices with ZnAF‐2DA, a membrane‐permeable zinc indicator. Intracellular ZnAF‐2 signal in the CA3 pyramidal cell layer was increased during delivery of tetanic stimuli to the dentate granule cell layer. This increase was completely blocked in the presence of CNQX, an AMPA/kainate receptor antagonist. These results suggest that free zinc is taken up into CA3 pyramidal cells via activation of AMPA/kainate receptors. The effect of free zinc levels in the CA3 pyramidal cells on the increase in intracellular calcium via Group I metabotropic glutamate receptors was examined by regional delivery of __t__ADA, a Group I metabotropic glutamate receptor agonist, to the stratum lucidum after blockade of AMPA/kainate receptor‐mediated calcium and zinc influx. Intracellular calcium orange signal in the CA3 pyramidal cell layer was increased by __t__ADA, whereas intracellular ZnAF‐2 signal was not increased even in the presence of 100 μM zinc, suggesting that __t__ADA induces calcium release from internal stores in CA3 pyramidal cells and is not involved in zinc uptake. The increase in calcium orange signal by __t__ADA was enhanced by perfusion with pyrithione, a zinc ionophore that decreased basal ZnAF‐2 signal in the CA3 pyramidal cell layer. It was blocked by perfusion with pyrithione and zinc that increased basal ZnAF‐2 signal. The present study indicates that the increase in free calcium levels via the metabotropic glutamate receptor pathway is inversely related to free zinc levels in CA3 pyramidal cells. © 2007 Wiley‐Liss, Inc.