title: Increased expression of the beta3 subunit of voltage-gated Na+ channels in the spinal cord of the SOD1G93A mouse.
abstract: Amyotrophic lateral sclerosis (ALS) is an adult-onset disease characterized by the progressive degeneration of motoneurons (MNs). Altered electrical properties have been described in familial and sporadic ALS patients. Cortical and spinal neurons cultured from the mutant Cu,Zn superoxide dismutase 1 (SOD1G93A) mouse, a murine model of ALS, exhibit a marked increase in the persistent Na+ currents. Here, we investigated the effects of the SOD1G93A mutation on the expression of the voltage-gated Na+ channel alpha subunit SCN8A (Nav1.6) and the beta subunits SCN1B (beta1), SCN2B (beta2), and SCN3B (beta3) in MNs of the spinal cord in presymptomatic (P75) and symptomatic (P120) mice. We observed a significant increase, within lamina IX, of the beta3 transcript and protein expression. On the other hand, the beta1 transcript was significantly decreased, in the same area, at the symptomatic stage, while the beta2 transcript levels were unaltered. The SCN8A transcript was significantly decreased at P120 in the whole spinal cord. These data suggest that the SOD1G93A mutation alters voltage-gated Na+ channel subunit expression. Moreover, the increased expression of the beta3 subunit support the hypothesis that altered persistent Na+ currents contribute to the hyperexcitability observed in the ALS-affected MNs.
authors: Molecular Neurobiology Unit, Experimental Neurology, Fondazione Santa Lucia, via del Fosso di Fiorano 64, 00179 Rome, Italy.
authors: Michele
authors: M
authors: Nutini
authors: Alida
authors: A
authors: Spalloni
authors: Fulvio
authors: F
authors: Florenzano
authors: Ruth E
authors: RE
authors: Westenbroek
authors: Claudia
authors: C
authors: Marini
authors: William A
authors: WA
authors: Catterall
authors: Giorgio
authors: G
authors: Bernardi
authors: Patrizia
authors: P
authors: Longone
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000473:pathology / Q000502:physiology; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D062548:Voltage-Gated Sodium Channel beta-2 Subunit; D062549:Voltage-Gated Sodium Channel beta-3 Subunit
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C540272:SCN2B protein, mouse; C561426:SCN3B protein, mouse; C524974:Scn1b protein, mouse; C491046:Scn8a protein, mouse; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D062548:Voltage-Gated Sodium Channel beta-2 Subunit; D062549:Voltage-Gated Sodium Channel beta-3 Subunit; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase