title: Persistent sodium currents contribute to Aβ1-42-induced hyperexcitation of hippocampal CA1 pyramidal neurons.
abstract: 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.
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Shuan-cheng
authors.initials: SC
authors.lastname: Ren
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Peng-zhi
authors.initials: PZ
authors.lastname: Chen
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Hui-hui
authors.initials: HH
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Mi
authors.affiliation: Department of Physiology and Pharmacology, The Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada. Electronic address: fxu@ucalgary.ca.
authors.forename: Fenglian
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, PR China. Electronic address: zhuzr2013@163.com.
authors.forename: Zhi-ru
authors.initials: ZR
authors.lastname: Zhu
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D015222:Sodium Channels; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Amyloid β; Hyperexcitation; Persistent sodium current; Riluzole