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Kaempferol 3-Rhamnoside on Glutamate Release from Rat Cerebrocortical Nerve Terminals Involves P/Q-Type $Ca^{2+}$ Channel and $Ca^{2+}$/Calmodulin-Dependent Protein Kinase II-Dependent Pathway Suppression
| Content Provider | MDPI |
|---|---|
| Author | Lin, Tzu-Kang Hung, Chi-Feng Weng, Jing-Ru Hsieh, Ting-Yang Wang, Su-Jane |
| Copyright Year | 2022 |
| Description | Excess synaptic glutamate release has pathological consequences, and the inhibition of glutamate release is crucial for neuroprotection. Kaempferol 3-rhamnoside (KR) is a flavonoid isolated from Schima superba with neuroprotective properties, and its effecton the release of glutamate from rat cerebrocortical nerve terminals was investigated. KR produced a concentration-dependent inhibition of 4-aminopyridine (4-AP)-evoked glutamate release with half-maximal inhibitory concentration value of 17 µM. The inhibition of glutamate release by KR was completely abolished by the omission of external $Ca^{2+}$ or the depletion of glutamate in synaptic vesicles, and it was unaffected by blocking carrier-mediated release. In addition, KR reduced the 4-AP-evoked increase in $Ca^{2+}$ concentration, while it did not affect 4-AP-evoked membrane potential depolarization. The application of selective antagonists of voltage-dependent $Ca^{2+}$ channels revealed that the KR-mediated inhibition of glutamate release involved the suppression of P/Q-type $Ca^{2+}$ channel activity. Furthermore, the inhibition of release was abolished by the calmodulin antagonist, W7, and $Ca^{2+}$/calmodulin-dependent protein kinase II (CaMKII) inhibitor, KN62, but not by the protein kinase A (PKA) inhibitor, H89, or the protein kinase C (PKC) inhibitor, GF109203X. We also found that KR reduced the 4-AP-induced increase in phosphorylation of CaMKII and its substrate synapsin I. Thus, the effect of KR on evoked glutamate release is likely linked to a decrease in P/Q-type $Ca^{2+}$ channel activity, as well as to the consequent reduction in the CaMKII/synapsin I pathway. |
| Starting Page | 1342 |
| e-ISSN | 14203049 |
| DOI | 10.3390/molecules27041342 |
| Journal | Molecules |
| Issue Number | 4 |
| Volume Number | 27 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-02-16 |
| Access Restriction | Open |
| Subject Keyword | Molecules Toxicology Kaempferol 3-rhamnoside Glutamate Release P/q-type Ca2+ Channels Ca2+/calmodulin-dependent Protein Kinase Ii Cerebrocortical Nerve Terminals |
| Content Type | Text |
| Resource Type | Article |
