Anticonvulsant effect of Rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy.
Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. Several studies have demonstrated that RIN has a significant anticonvulsant effect in many types of epilepsy models in vivo. However, the mechanisms of the anticonvulsant effect remain elusive. Using combined methods of behavioral testing, immunofluorescence and electrophysiological recordings, we characterized the anticonvulsant effect of RIN in a pilocarpine-induced status epilepticus (SE) rat model of temporal lobe epilepsy (TLE) and investigated the underlying cellular mechanisms. In one set of experiments, rats received RIN treatment prior to pilocarpine injection. In a second set of experiments, rats received RIN treatment following the onset of stage 3 seizures. Pretreatment and posttreatment with RIN effectively reduced the seizure severity in the acute phase of TLE. Furthermore, RIN protected medial entorhinal cortex (mEC) layer III neurons from neuronal death and terminated spontaneous epileptiform discharge of mEC layer II neurons in SE-experienced rats. Whole-cell voltage-clamp recordings indicated that RIN inhibited neuronal hyperexcitability via inhibition of the persistent sodium current (INaP) and NMDA receptor current. Immunofluorescence experiments also demonstrated that RIN rectified the pilocarpine-induced upregulation of Nav1.6 and NR2B protein expression. In conclusion, our results identified RIN as an anticonvulsant agent that inhibited ictal discharge via INapand NMDA receptor current inhibition.
Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China; Department of Physiology, Third Military Medical University, Chongqing, China; The Fifth Camp of Cadet Brigade, Third Military Medical University, Chongqing, China.
Hui
H
Shao
Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China.
Yang
Y
Yang
Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China.
Ze
Z
Mi
Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China.
Guang-Xi
GX
Zhu
Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China.
Ai-Ping
AP
Qi
Department of Chemistry, Faculty of Pharmacy, Third Military Medical University, Chongqing, China.
Wei-Gang
WG
Ji
Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China; Department of Physiology, Third Military Medical University, Chongqing, China. Electronic address: zhuzr2013@163.com.
Zhi-Ru
ZR
Zhu
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D000078183:Oxindoles; D010862:Pilocarpine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced
D000927:Anticonvulsants; D026121:Indole Alkaloids; D000078183:Oxindoles; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; C052714:rhyncophylline; D012964:Sodium
NMDA receptor current; Rhynchophylline; entorhinal cortex; persistent sodium current; temporal lobe epilepsy