Referenced in: none

Automatically associated channels: Cav2.1 , Cav2.2

Title: Apigenin, a natural flavonoid, inhibits glutamate release in the rat hippocampus.

Authors: Chia Ying Chang, Tzu Yu Lin, Cheng Wei Lu, Chia Chuan Wang, Ying Chou Wang, Shang Shing Peter Chou, Su Jane Wang

Journal, date & volume: Eur. J. Pharmacol., 2015 Sep 5 , 762, 72-81

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26007643

Abstract
The purpose of this study was to examine the effect and mechanism of apigenin, a natural flavonoid, on glutamate release in the rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), apigenin inhibited glutamate release and the elevation of the cytosolic free Ca(2+) concentration evoked by 4-aminopyridine, whereas it had no effect on 4-aminopyridine-mediated depolarization and Na(+) influx. The apigenin-mediated inhibition of evoked glutamate release was prevented by chelating the extracellular Ca(2+) ions and blocking Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel activity. Furthermore, we determined that gamma-aminobutyric acid type A (GABAA) receptors are present in the hippocampal nerve terminals because they are colocalized with the presynaptic marker synaptophysin. However, the effect of apigenin on 4-aminopyridine-evoked glutamate release from synaptosomes was unaffected by the GABAA receptor antagonists SR95531 and bicuculline. Furthermore, in slice preparations, whole-cell patch-clamp experiments showed that apigenin reduced the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, suggesting a presynaptic mechanism. On the basis of these results, we suggested that apigenin exerts its presynaptic inhibition probably by reducing Ca(2+) entry mediated by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, thereby inhibiting glutamate release from the rat hippocampal nerve terminals.