TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
| العنوان: | TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons |
|---|---|
| المؤلفون: | Ki Bum Um, Suyun Hahn, Lutz Birnbaumer, Yoon Je Lee, So Woon Kim, Hyunjin Kim, Myoung Kyu Park |
| المصدر: | eLife. 2021 eLife, Vol 10 (2021) Repositorio Institucional (UCA) Pontificia Universidad Católica Argentina instacron:UCA |
| بيانات النشر: | eLife, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, QH301-705.5, Science, Action Potentials, Substantia nigra, TRPC3, Ion Channels, General Biochemistry, Genetics and Molecular Biology, Midbrain, Mice, pacemaker channels, Biological Clocks, Dopamine, medicine, Animals, Biology (General), DOPAMINA, Ion channel, TRPC Cation Channels, Mice, Knockout, Neurons, NEURONAS, dopaminergic neurons, General Immunology and Microbiology, NALCN, Chemistry, General Neuroscience, Dopaminergic, SISTEMA NERVIOSO CENTRAL, Membrane Proteins, Depolarization, General Medicine, medicine.anatomical_structure, nervous system, substantia nigra, Medicine, Female, pacemaking, Neuron, Neuroscience, medicine.drug |
| الوصف: | Fil: Um, Ki Bum. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea Fil: Hahn, Suyun. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea Fil: Kim, So Woon. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea Fil: Lee, Yoon Je. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Kim, Hyun Jin. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea Fil: Kim, Hyun Jin. Centro Médico Samsung. Instituto de Investigación Biomédica de Samsung; República de Corea Fil: Park, Myoung Kyu. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea Fil: Park, Myoung Kyu. Centro Médico Samsung. Instituto de Investigación Biomédica de Samsung; República de Corea 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2154bde7812c4d4f5426b05cce15afdTest https://repositorio.uca.edu.ar/handle/123456789/13952Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d2154bde7812c4d4f5426b05cce15afd |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |