CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Ca(v)3.2 T-type calcium channel activity and reticular thalamic neuron firing
| Autor: | Yuriy Rzhepetskyy, Joanna Lazniewska, Norbert Weiss, Iulia Blesneac, Roger Pamphlett |
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| Přispěvatelé: | Rzhepetskyy, Yuriy, Lazniewska, Joanna, Blesneac, Iulia, Pamphlett, Roger, Weiss, Norbert |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Biochemistry & Molecular Biology amyotrophic lateral sclerosis Thalamus Mutation Missense Biophysics Biology Transfection Biochemistry Cell Line Calcium Channels T-Type 03 medical and health sciences 0302 clinical medicine biophysics medicine CACNA1H Humans Missense mutation Amyotrophic lateral sclerosis Cav3.2 channel Neurons Calcium channel missense mutation Amyotrophic Lateral Sclerosis T-type calcium channel medicine.disease Spinal cord 030104 developmental biology medicine.anatomical_structure T-type channel Reticular connective tissue biology.protein calcium channel ALS Neuroscience 030217 neurology & neurosurgery Research Paper |
| Popis: | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. In a recent study by Steinberg and colleagues, 2 recessive missense mutations were identified in the Ca(v)3.2 T-type calcium channel gene (CACNA1H), in a family with an affected proband (early onset, long duration ALS) and 2 unaffected parents. We have introduced and functionally characterized these mutations using transiently expressed human Ca(v)3.2 channels in tsA-201 cells. Both of these mutations produced mild but significant changes on T-type channel activity that are consistent with a loss of channel function. Computer modeling in thalamic reticular neurons suggested that these mutations result in decreased neuronal excitability of thalamic structures. Taken together, these findings implicate CACNA1H as a susceptibility gene in amyotrophic lateral sclerosis. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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