TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
Abstract: Midbrain dopamine (DA) neurons are slow pacemakers that maintain extracellular DA levels. During the interspike intervals, subthreshold slow depolarization underlies autonomous pacemaking and determines its rate. However, the ion channels that determine slow depolarization are unknown....
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| Autores principales: | , , , , , , |
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| Otros Autores: | |
| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
eLife
2022
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| Materias: | |
| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/13952 |
| Aporte de: |
| Sumario: | Abstract: Midbrain dopamine (DA) neurons are slow pacemakers that maintain extracellular DA
levels. During the interspike intervals, subthreshold slow depolarization underlies autonomous pacemaking
and determines its rate. However, the ion channels that determine slow depolarization are
unknown. Here we show that TRPC3 and NALCN channels together form sustained inward currents
responsible for the slow depolarization of nigral DA neurons. Specific TRPC3 channel blockade
completely blocked DA neuron pacemaking, but the pacemaking activity in TRPC3 knock-out
(KO)
mice was perfectly normal, suggesting the presence of compensating ion channels. Blocking NALCN
channels abolished pacemaking in both TRPC3 KO and wild-type
mice. The NALCN current and
mRNA and protein expression are increased in TRPC3 KO mice, indicating that NALCN compensates
for TRPC3 currents. In normal conditions, TRPC3 and NALCN contribute equally to slow depolarization.
Therefore, we conclude that TRPC3 and NALCN are two major leak channels that drive
robust pacemaking in nigral DA neurons. |
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