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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 Cav3.2 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 Cav3.2 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.

Original publication

DOI

10.1080/19336950.2016.1204497

Type

Journal article

Journal

Channels (Austin)

Publication Date

11/2016

Volume

10

Pages

466 - 477

Keywords

ALS, CACNA1H, Cav3.2 channel, T-type channel, amyotrophic lateral sclerosis, biophysics, calcium channel, missense mutation, Amyotrophic Lateral Sclerosis, Calcium Channels, T-Type, Cell Line, Humans, Mutation, Missense, Neurons, Thalamus, Transfection