期刊
CEREBRAL CORTEX
卷 32, 期 14, 页码 2907-2923出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhab390
关键词
hippocampus; kainate receptors; Kv7; M-current
资金
- Centre National de la Recherche Scientifique
- French Government
- French Embassy in Poland
- National Science Center (Poland) [2015/19/D/NZ7/02402, 2013/08/M/NZ3/00655]
Kainate receptors (KARs) play a crucial role in regulating synaptic circuits through ionotropic or metabotropic mechanisms. This study reveals that the acute convulsive effect of kainate is primarily dependent on GluK2/GluK5 containing KARs, while the convulsive activity induced by pilocarpine and pentylenetetrazol is not affected by the absence of KARs. Interestingly, the genetic inactivation of GluK2 increases susceptibility to acute pilocarpine-induced seizures.
Kainate receptors (KARs) are key regulators of synaptic circuits by acting at pre- and postsynaptic sites through either ionotropic or metabotropic actions. KARs can be activated by kainate, a potent neurotoxin, which induces acute convulsions. Here, we report that the acute convulsive effect of kainate mostly depends on GluK2/GluK5 containing KARs. By contrast, the acute convulsive activity of pilocarpine and pentylenetetrazol is not alleviated in the absence of KARs. Unexpectedly, the genetic inactivation of GluK2 rather confers increased susceptibility to acute pilocarpine-induced seizures. The mechanism involves an enhanced excitability of GluK2(-/-) CA3 pyramidal cells compared with controls upon pilocarpine application. Finally, we uncover that the absence of GluK2 increases pilocarpine modulation of Kv7/M currents. Taken together, our findings reveal that GluK2-containing KARs can control the excitability of hippocampal circuits through interaction with the neuromodulatory cholinergic system.
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