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This Article Full Text Full Text (PDF) All Versions of this Article: 96/6/3314    most recent 00566.2006v2 00566.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Zona, C. Articles by Carunchio, I. Search for Related Content PubMed PubMed Citation Articles by Zona, C. Articles by Carunchio, I.

Voltage-Dependent Sodium Channels in Spinal Cord Motor Neurons Display Rapid Recovery From Fast Inactivation in a Mouse Model of Amyotrophic Lateral Sclerosis

¹Department of Neuroscience, University of Rome; and ²Fondazione S. Lucia, Centro Europeo di Ricerca sul Cervello, Rome, Italy

Submitted 29 May 2006; accepted in final form 31 July 2006

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a substantial loss of motor neurons in the spinal cord, brain stem, and motor cortex. Previous evidence showed that in a mouse model of a familial form of ALS expressing high levels of the human mutated protein Cu,Zn superoxide dismutase (Gly⁹³Ala, G93A), the firing properties of single motor neurons are altered to induce neuronal hyperexcitability. To determine whether the functionality of the macroscopic voltage-dependent Na⁺ currents is modified in G93A motor neurons, in the present work their physiological properties were examined. The voltage-dependent sodium channels were studied in dissociated motor neurons in culture from nontransgenic mice (Control), from transgenic mice expressing high levels of the human wild-type protein [superoxide dismutase 1 (SOD1)], and from G93A mice, using the whole cell configuration of the patch-clamp recording technique. The voltage dependency of activation and of steady-state inactivation, the kinetics of fast inactivation and slow inactivation of the voltage-dependent Na⁺ channels were not modified in the mutated mice. Conversely, the recovery from fast inactivation was significantly faster in G93A motor neurons than that in Control and SOD1. The recovery from fast inactivation was still significantly faster in G93A motor neurons exposed for different times (3–48 h) and concentrations (5–500 µM) to edaravone, a free-radical scavenger. Clarification of the importance of these changes in membrane ion channel functionality may have diagnostic and therapeutic implications in the pathogenesis of ALS.