Mechanism of Manganese Dysregulation of Dopamine Neuronal Activity.

ABSTRACT: Manganese exposure produces Parkinson's-like neurologic symptoms, suggesting a selective dysregulation of dopamine transmission. It is unknown, however, how manganese accumulates in dopaminergic brain regions or how it regulates the activity of dopamine neurons. Our in vivo studies in male C57BLJ mice suggest that manganese accumulates in dopamine neurons of the VTA and substantia nigra via nifedipine-sensitive Ca²⁺ channels. Manganese produces a Ca²⁺ channel-mediated current, which increases neurotransmitter release and rhythmic firing activity of dopamine neurons. These increases are prevented by blockade of Ca²⁺ channels and depend on downstream recruitment of Ca²⁺-activated potassium channels to the plasma membrane. These findings demo

SUBMITTER: Lin M 

PROVIDER: S-EPMC7380961 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature