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Título : TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
Autor : Um, Ki Bum 
Hahn, Suyun 
Kim, So Woon 
Lee, Yoon Je 
Birnbaumer, Lutz 
Kim, Hyun Jin 
Park, Myoung Kyu 
Palabras clave : TRPC3NALCNNEURONASDOPAMINASISTEMA NERVIOSO CENTRAL
Fecha de publicación : 2021
Editorial : eLife
Cita : Um, K. B. et al. TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons [en línea]. eLife. 2021. doi: 10.7554/eLife.70920. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/13952
Resumen : 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.
URI : https://repositorio.uca.edu.ar/handle/123456789/13952
Disciplina: MEDICINA
DOI: 10.7554/eLife.70920
Derechos: Acceso abierto
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