Persistent sodium currents contribute to Aβ1-42-induced hyperexcitation of hippocampal CA1 pyramidal neurons

• We investigated the effects of soluble Aβ1-42 on neuronal excitability.
• Soluble Aβ1-42 increased the mean frequency of hippocampal spontaneous discharges.
• Soluble Aβ1-42 also increased the amplitude of persistent sodium current.
• Riluzole inhibited the Aβ1-42-induced neuronal hyperexcitation.

Patients with Alzheimer's disease (AD) have elevated incidence of epilepsy. Moreover, neuronal hyperexcitation occurs in transgenic mouse models overexpressing amyloid precursor protein and its pathogenic product, amyloid β protein (Aβ). However, the cellular mechanisms of how Aβ causes neuronal hyperexcitation are largely unknown. We hypothesize that the persistent sodium current (INaP), a subthreshold sodium current that can increase neuronal excitability, may in part account for the Aβ-induced neuronal hyperexcitation. The present study was designed to evaluate the involvement of INaP in Aβ-induced hyperexcitation of hippocampal CA1 pyramidal neurons using a whole-cell patch-clamp recording technique. Our results showed that bath application of soluble Aβ1-42 increased neuronal excitability in a concentration-dependent manner. Soluble Aβ1-42 also increased the amplitude of INaP without significantly affecting its activation properties. In the presence of riluzole (RLZ), an antagonist of INaP, the Aβ1-42-induced neuronal hyperexcitation and INaP augmentation were significantly inhibited. These findings suggest that soluble Aβ1-42 may induce neuronal hyperexcitation by increasing the amplitude of INaP and that RLZ can inhibit the Aβ1-42-induced abnormal neuronal activity.