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: Um, Ki Bum, Hahn, Suyun, Kim, So Woon, Lee, Yoon Je, Birnbaumer, Lutz, Kim, Hyun Jin, Park, Myoung Kyu
Otros Autores: 0000-0002-4882-5736
Formato: Artículo
Lenguaje:Inglés
Publicado: eLife 2022
Materias:
TRPC3
NALCN
NEURONAS
DOPAMINA
SISTEMA NERVIOSO CENTRAL
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/13952
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-13952
record_format dspace
spelling I33-R139-123456789-139522023-11-22T22:06:43Z TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons Um, Ki Bum Hahn, Suyun Kim, So Woon Lee, Yoon Je Birnbaumer, Lutz Kim, Hyun Jin Park, Myoung Kyu 0000-0002-4882-5736 TRPC3 NALCN NEURONAS DOPAMINA SISTEMA NERVIOSO CENTRAL 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. 2022-05-13T10:45:55Z 2022-05-13T10:45:55Z 2021 Artículo 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 https://repositorio.uca.edu.ar/handle/123456789/13952 10.7554/eLife.70920 34409942 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf eLife eLife. 2021
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic TRPC3
NALCN
NEURONAS
DOPAMINA
SISTEMA NERVIOSO CENTRAL
spellingShingle TRPC3
NALCN
NEURONAS
DOPAMINA
SISTEMA NERVIOSO CENTRAL
Um, Ki Bum
Hahn, Suyun
Kim, So Woon
Lee, Yoon Je
Birnbaumer, Lutz
Kim, Hyun Jin
Park, Myoung Kyu
TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
topic_facet TRPC3
NALCN
NEURONAS
DOPAMINA
SISTEMA NERVIOSO CENTRAL
description 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.
author2 0000-0002-4882-5736
author_facet 0000-0002-4882-5736
Um, Ki Bum
Hahn, Suyun
Kim, So Woon
Lee, Yoon Je
Birnbaumer, Lutz
Kim, Hyun Jin
Park, Myoung Kyu
format Artículo
author Um, Ki Bum
Hahn, Suyun
Kim, So Woon
Lee, Yoon Je
Birnbaumer, Lutz
Kim, Hyun Jin
Park, Myoung Kyu
author_sort Um, Ki Bum
title TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_short TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_full TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_fullStr TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_full_unstemmed TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_sort trpc3 and nalcn channels drive pacemaking in substantia nigra dopaminergic neurons
publisher eLife
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/13952
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AT hahnsuyun trpc3andnalcnchannelsdrivepacemakinginsubstantianigradopaminergicneurons
AT kimsowoon trpc3andnalcnchannelsdrivepacemakinginsubstantianigradopaminergicneurons
AT leeyoonje trpc3andnalcnchannelsdrivepacemakinginsubstantianigradopaminergicneurons
AT birnbaumerlutz trpc3andnalcnchannelsdrivepacemakinginsubstantianigradopaminergicneurons
AT kimhyunjin trpc3andnalcnchannelsdrivepacemakinginsubstantianigradopaminergicneurons
AT parkmyoungkyu trpc3andnalcnchannelsdrivepacemakinginsubstantianigradopaminergicneurons
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