Rzhepetskyy, Y., Lazniewska, J., Blesneac, I., Pamphlett, R., & Weiss, N. (2016). CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Cav3.2 T-type calcium channel activity and reticular thalamic neuron firing. Channels.
Rzhepetskyy, Y., J. Lazniewska, I. Blesneac, R. Pamphlett, and N. Weiss. “CACNA1H Missense Mutations Associated with Amyotrophic Lateral Sclerosis Alter Cav3.2 T-Type Calcium Channel Activity and Reticular Thalamic Neuron Firing.” Channels (2016).
Rzhepetskyy, Y., et al. “CACNA1H Missense Mutations Associated with Amyotrophic Lateral Sclerosis Alter Cav3.2 T-Type Calcium Channel Activity and Reticular Thalamic Neuron Firing.” Channels, 2016.
ABSTRACT 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.