CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Ca(v)3.2 T-type calcium channel activity and reticular thalamic neuron firing

0464731 - ÚOCHB 2017 RIV US eng J - Článek v odborném periodiku
Rzhepetskyy, Yuriy - Lazniewska, Joanna - Blesneac, I. - Pamphlett, R. - Weiss, Norbert
CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Ca(v)3.2 T-type calcium channel activity and reticular thalamic neuron firing.
Channels. Roč. 10, č. 6 (2016), s. 466-477. ISSN 1933-6950. E-ISSN 1933-6969
Grant CEP: GA ČR GA15-13556S; GA MŠMT 7AMB15FR015
Institucionální podpora: RVO:61388963
Klíčová slova: ALS * amyotrophic lateral sclerosis * biophysics * CACNA1H * Ca(v)3 * 2 channel
Kód oboru RIV: CE - Biochemie
Impakt faktor: 2.042, rok: 2016

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.
Trvalý link: http://hdl.handle.net/11104/0263509