LuAE98134是电压门控钠通道(voltage-gatedsodiumchannels)的激活剂，作为Nav1.1通道的部分选择性激活剂。LuAE98134也可以增加Nav1.2和Nav1.5通道的活性，但对Nav1.4、Nav1.6和Nav1.7通道活性无明显影响。LuAE98134可用于分析Nav1.1通道在各种中枢神经系统疾病中的病理生理功能，如精神分裂症等。
Lu AE98134, an activator of voltage-gated sodium channels, acts as a partly selective Nav1.1 channels positive modulator. Lu AE98134 also increases the activity of Nav1.2 and Nav1.5 channels but not of Nav1.4, Nav1.6 and Nav1.7 channels. Lu AE98134 can be used to analyze pathophysiological functions of the Nav1.1 channel in various central nervous system diseases, including cognitive restoring in schizophrenia, et al[1].
Lu AE98134 (30 μM) promotes the current mediated by Navv1.1 channel, and it activates Nav1.5 and to a lesser extent Nav1.2 but has no effect on Nav1.4, Nav1.6 and Nav1.7 currents in HEK cells expressing Nav1.1, Nav1.2, Nav1.6, Nav1.5, and Nav1.7 by step-wise depolarizing voltages using the whole-cell patchclamp configuration[1]. Lu AE98134 (30 μM) increases the excitability of FSINs by decreasing the threshold for action potentials.Intracellular depolarizing current pulses evokes repetitive firing of action potentials at frequencies, additionally, Lu AE98134 increases the excitability since each current pulse generated a higher number of spikes (163 spikes in control; and 230 spikes in Lu AE98134)[1].
The fast spiking inhibitory interneurons (FSINs) from Dlx5/6+/- animals exhibit abnormal excitability because of a more depolarized spike threshold and broader action potentials.Lu AE98134 (30 μM) increases the excitability of FSINs neurons from normal and Dlx5/6+/- animals by modulating several parameters characteristic for NaV1.1 channels. The selective activation of FSINs by Lu AE98134 restores cognitive flexibility in adult Dlx5/6+/- mice[1].
[1]. Nadia Lyb?l von Schoubye, et al. The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6 +/- mice. Neurosci Lett. 2018 Jan 1;662:29-35.
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