title: Partial block by riluzole of muscle sodium channels in myotubes from amyotrophic lateral sclerosis patients.
abstract: Denervated muscles undergo fibrillations due to spontaneous activation of voltage-gated sodium (Na(+)) channels generating action potentials. Fibrillations also occur in patients with amyotrophic lateral sclerosis (ALS). Riluzole, the only approved drug for ALS treatment, blocks voltage-gated Na(+) channels, but its effects on muscle Na(+) channels and fibrillations are yet poorly characterized. Using patch-clamp technique, we studied riluzole effect on Na(+) channels in cultured myotubes from ALS patients. Needle electromyography was used to study fibrillation potentials (Fibs) in ALS patients during riluzole treatment and after one week of suspension. Patients were clinically characterized in all recording sessions. In myotubes, riluzole (1 μM, a therapeutic concentration) reduced Na(+) current by 20%. The rate of rise and amplitude of spikes evoked by depolarizing stimuli were also reduced. Fibs were detected in all patients tested during riluzole treatment and riluzole washout had no univocal effect. Our study indicates that, in human myotubes, riluzole partially blocks Na(+) currents and affects action potentials but does not prevent firing. In line with this in vitro finding, muscle Fibs in ALS patients appear to be largely unaffected by riluzole.
authors.affiliation: Department of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Deflorio
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università 30, 00185 Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Onesti
authors.affiliation: Department of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Clotilde
authors.identifier: 0000-0001-9910-5731
authors.initials: C
authors.lastname: Lauro
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università 30, 00185 Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tartaglia
authors.affiliation: Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Aldo
authors.identifier: 0000-0003-1863-6202
authors.initials: A
authors.lastname: Giovannelli
authors.affiliation: Department of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy ; IIT@Sapienza, Center for Life Nano Science, Viale Regina Elena 291, 00161 Roma, Italy ; IRCCS Neuromed, 86077 Pozzilli, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Limatola
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università 30, 00185 Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Inghilleri
authors.affiliation: Department of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Francesca
authors.identifier: 0000-0002-0169-8397
authors.initials: F
authors.lastname: Grassi