Cav2.3 channels contribute to dopaminergic neuron loss in a model of Parkinson's disease.

ABSTRACT: Degeneration of dopaminergic neurons in the substantia nigra causes the motor symptoms of Parkinson's disease. The mechanisms underlying this age-dependent and region-selective neurodegeneration remain unclear. Here we identify Cav2.3 channels as regulators of nigral neuronal viability. Cav2.3 transcripts were more abundant than other voltage-gated Ca²⁺ channels in mouse nigral neurons and upregulated during aging. Plasmalemmal Cav2.3 protein was higher than in dopaminergic neurons of the ventral tegmental area, which do not degenerate in Parkinson's disease. Cav2.3 knockout reduced activity-associated nigral somatic Ca²⁺ signals and Ca²⁺-dependent after-hyperpolarizations, and afforded full protection from degeneration in vivo in a neurotoxin Parkinson's m

SUBMITTER: Benkert J 

PROVIDER: S-EPMC6841684 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature