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CNS & Neurological Disorders - Drug Targets


ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Research Article

Activation of Kir2.3 Channels by Tenidap Suppresses Epileptiform Burst Discharges in Cultured Hippocampal Neurons

Author(s): Xunyi Wu*, Zhiyun Chen, Wanbing Sun, Guoxiang Wang, Lu Zhang, Yuwen Zhang, Kai Zang and Yun Wang*

Volume 18, Issue 8, 2019

Page: [621 - 630] Pages: 10

DOI: 10.2174/1871527318666190807122623

Price: $65


Background & Objective: Tenidap, a selective human inwardly rectifying potassium (Kir) 2.3 channel opener, has been reported to have antiepileptic effect in the pilocarpine temporal lobe epilepsy rat model in our previous study. However, the effect of tenidap on neurons and its relationship with the epileptiform bursting charges in neuron is still required to be explored.

Methods: In this study, cyclothiazide (CTZ) induced cultured hippocampal neuron epileptic model was used to study the antiepileptic effect of tenidap and the relationship between Kir2.3 channel and the neuronal epileptiform burst.

Results: Patch clamp recording showed that both acute (2h) and chronic (48h) CTZ pre-treatment all significantly induced robust epileptiform burst activities in cultured hippocampal neurons, and tenidap acutely application inhibited this highly synchronized abnormal activities. The effect of tenidap is likely due to increased activity of Kir2.3 channels, since tenidap significantly enhanced kir current recorded from those neurons. In addition, neurons overexpressing Kir2.3 channels, by transfection with Kir2.3 plasmid, showed a significant large increase of the Kir current, prevented CTZ treatment to induce epileptiform burst discharge.

Conclusion: Our current study demonstrated that over activation of Kir2.3 channel in hippocampal neurons could positively interference with epileptiform burst activities, and tenidap, as a selective Kir2.3 channel opener, could be a potential candidate for seizure therapy.

Keywords: Tenidap, potassium channel, Kir2.3, epilepsy, neurological disorder, epileptiform burst firing.

Graphical Abstract
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