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• W4282946922 abstract "The low-threshold L-type calcium channel Cav1.3 accelerates the pacemaker rate in the heart, but its functional role for the extended dynamic range of neuronal firing is still unresolved. Here, we show that Cav1.3 calcium channels act as unexpectedly simple, full-range linear amplifiers of firing rates for lateral dopamine substantia nigra (DA SN) neurons in mice. This means that they boost in vitro or in vivo firing frequencies between 2 and 50 hertz by about 30%. Furthermore, we demonstrate that clinically relevant, low nanomolar concentrations of the L-type channel inhibitor isradipine selectively reduce the in vivo firing activity of these nigrostriatal DA SN neurons at therapeutic plasma concentrations. Thus, our study identifies the pacemaker function of neuronal Cav1.3 channels and provides direct evidence that repurposing dihydropyridines such as isradipine is feasible to selectively modulate the in vivo activity of highly vulnerable DA SN subpopulations in Parkinson's disease." @default.
• W4282946922 created "2022-06-16" @default.
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• W4282946922 date "2022-06-10" @default.
• W4282946922 modified "2023-10-16" @default.
• W4282946922 title "Ca _v 1.3 calcium channels are full-range linear amplifiers of firing frequencies in lateral DA SN neurons" @default.
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• W4282946922 doi "https://doi.org/10.1126/sciadv.abm4560" @default.
• W4282946922 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35675413" @default.
• W4282946922 hasPublicationYear "2022" @default.
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