Tenidap suppresses epileptiform burst discharges in cultured hippocampal neurons by activation of Kir2.3 channels

CNS & Neurological Disorders Drug Targets
Xun-Yi WuYun Wang

Abstract

Tenidap, a selective human Kir2.3 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. 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. 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. Our current study demonstrated that over activation of kir2.3 channel i...Continue Reading

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May 19, 2020·CNS & Neurological Disorders Drug Targets·Chryssa PourzitakiVasilios K Kimiskidis
Oct 30, 2021·Journal of Neuroscience Research·Enes AkyuzYam Nath Paudel

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