LU AE98134

Lu AE98134 (30 μM) promotes the current mediated by Nav _v 1.1 channel, and it activates Na _v 1.5 and to a lesser extent Na _v 1.2 but has no effect on Na _v 1.4, Na _v 1.6 and Na _v 1.7 currents in HEK cells expressing Na _v 1.1, Na _v 1.2, Na _v 1.6, Na _v 1.5, and Na _v 1.7 by step-wise depolarizing voltages using the whole-cell patchclamp configuration. 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).

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 NaV _1.1 channels. The selective activation of FSINs by Lu AE98134 restores cognitive flexibility in adult Dlx5/6 ^+/− mice.