43 / 2021-07-29 14:13:20

Inhibitory effect of KCNQ channel openers on epileptiform discharge in rat brain slices

KCNQ channel opener，Epilepsy，Patch clamp

Background：Epilepsy is a common neurological disease, characterized by abnormal and repeated discharge of brain neurons. Currently, drug control is the main means of treatment for epilepsy, but about 30% of patients are not sensitive to existing antiepileptic drugs and cannot be effectively treated, so the emergence of new antiepileptic drugs is needed.As a member of voltage-gated potassium ion channels, KCNQ channel plays an important role in regulating the excitability of brain neurons, such as the maintenance of cell membrane potential, the formation of action potential （AP）and the release of neurotransmitters, making KCNQ channel a new target for the research and development of antiepileptic drugs.Based on the structure of TRG, we developed a new KCNQ channel opener QO-83 compound.

Purpose: To investigate the effect of KCNQ channel opener QO-83 compound on epileptic discharge in rat hippocampal pyramidal cells.

Methods: Hippocampal slices were prepared from 4-6 weeks male SD rats, and the spontaneous firing activity of neurons were observed with whole cell patch clamp technique. The change of APs induced by step current injection was analyzed after the administration of QO-83 compound. Mg²⁺-free cerebrospinal fluid was used to induce epileptiform discharge, to observe changes in neuronal discharge activity compared pre- and post-administration QO-83 compound. 

Results: The hippocampal vertebral neurons are not easy to produce spontaneous discharge, and most of them are in a resting state. Evoked APs following current injection in different steps ranging from 0 to 180 PA. Set the 1μＭ, 5μＭ, 10μＭ three concentration gradient, compare QO-83 with RTG in the 5μＭ and 10μＭ concentrations, there was no significant difference on the number of APs break. However, at the concentration of 1μＭ, the inhibitory effect of QO-83 compound was significantly higher than that of RTG(P<0.05). In addition, compared with RTG(1μＭ), QO-83(1μＭ) compound significantly prolonged the after hyperpolarization time (P<0.05). Otherwise, after Mg²⁺-free ACSF perfusion, 5μM QO-83 compound significantly inhibited epileptic discharge (P<0.05).