Partial Block by Riluzole of Muscle Sodium Channels in Myotubes from Amyotrophic Lateral Sclerosis Patients
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+ chan...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Neurology Research International |
| Online Access: | http://dx.doi.org/10.1155/2014/946073 |
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| author | Cristina Deflorio Emanuela Onesti Clotilde Lauro Giorgio Tartaglia Aldo Giovannelli Cristina Limatola Maurizio Inghilleri Francesca Grassi |
| author_facet | Cristina Deflorio Emanuela Onesti Clotilde Lauro Giorgio Tartaglia Aldo Giovannelli Cristina Limatola Maurizio Inghilleri Francesca Grassi |
| author_sort | Cristina Deflorio |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2f1f8dd58c444a119d0f4d51c0bf26c3 |
| institution | Kabale University |
| issn | 2090-1852 2090-1860 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neurology Research International |
| spelling | doaj-art-2f1f8dd58c444a119d0f4d51c0bf26c32025-02-03T06:12:44ZengWileyNeurology Research International2090-18522090-18602014-01-01201410.1155/2014/946073946073Partial Block by Riluzole of Muscle Sodium Channels in Myotubes from Amyotrophic Lateral Sclerosis PatientsCristina Deflorio0Emanuela Onesti1Clotilde Lauro2Giorgio Tartaglia3Aldo Giovannelli4Cristina Limatola5Maurizio Inghilleri6Francesca Grassi7Department of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Neurology and Psychiatry, Sapienza University, Viale dell’Università 30, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Neurology and Psychiatry, Sapienza University, Viale dell’Università 30, 00185 Rome, ItalyDepartment of Applied Clinical and Biotechnological Sciences, University of L’Aquila, Via Vetoio, Coppito 2, 67100 L’Aquila, ItalyDepartment of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Neurology and Psychiatry, Sapienza University, Viale dell’Università 30, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, ItalyDenervated 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.http://dx.doi.org/10.1155/2014/946073 |
| spellingShingle | Cristina Deflorio Emanuela Onesti Clotilde Lauro Giorgio Tartaglia Aldo Giovannelli Cristina Limatola Maurizio Inghilleri Francesca Grassi Partial Block by Riluzole of Muscle Sodium Channels in Myotubes from Amyotrophic Lateral Sclerosis Patients Neurology Research International |
| title | Partial Block by Riluzole of Muscle Sodium Channels in Myotubes from Amyotrophic Lateral Sclerosis Patients |
| title_full | Partial Block by Riluzole of Muscle Sodium Channels in Myotubes from Amyotrophic Lateral Sclerosis Patients |
| title_fullStr | Partial Block by Riluzole of Muscle Sodium Channels in Myotubes from Amyotrophic Lateral Sclerosis Patients |
| title_full_unstemmed | Partial Block by Riluzole of Muscle Sodium Channels in Myotubes from Amyotrophic Lateral Sclerosis Patients |
| title_short | Partial Block by Riluzole of Muscle Sodium Channels in Myotubes from Amyotrophic Lateral Sclerosis Patients |
| title_sort | partial block by riluzole of muscle sodium channels in myotubes from amyotrophic lateral sclerosis patients |
| url | http://dx.doi.org/10.1155/2014/946073 |
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