Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area
Dopaminergic neurons in the ventral tegmental area (VTA) encode behavioral patterns important in reward and drug addiction as well as in emotional disorders. These functions of dopamine neurons are directly related to the release of dopamine in the targeted regions of the brain which are, thus, cont...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00557/full |
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| author | Min Su Min Su Min Su Li Li Li Li Li Li Jing Wang Jing Wang Jing Wang Jing Wang Hui Sun Hui Sun Hui Sun Ludi Zhang Ludi Zhang Ludi Zhang Chen Zhao Chen Zhao Chen Zhao Ying Xie Nikita Gamper Nikita Gamper Nikita Gamper Nikita Gamper Xiaona Du Xiaona Du Xiaona Du Hailin Zhang Hailin Zhang Hailin Zhang |
| author_facet | Min Su Min Su Min Su Li Li Li Li Li Li Jing Wang Jing Wang Jing Wang Jing Wang Hui Sun Hui Sun Hui Sun Ludi Zhang Ludi Zhang Ludi Zhang Chen Zhao Chen Zhao Chen Zhao Ying Xie Nikita Gamper Nikita Gamper Nikita Gamper Nikita Gamper Xiaona Du Xiaona Du Xiaona Du Hailin Zhang Hailin Zhang Hailin Zhang |
| author_sort | Min Su |
| collection | DOAJ |
| description | Dopaminergic neurons in the ventral tegmental area (VTA) encode behavioral patterns important in reward and drug addiction as well as in emotional disorders. These functions of dopamine neurons are directly related to the release of dopamine in the targeted regions of the brain which are, thus, controlled by the excitability of dopamine neurons. One mechanism for modulation of dopamine neuronal excitability is mediated by the auto dopamine type 2 (D2) receptors, through activation of a Kir3/GIRK K+ channel which inhibits the firing of dopamine neurons. In this study, we provide evidence that Kv7.4, in addition to Kir3.2 channels, contributes to dopamine (DA)-mediated auto-inhibition of DA activity projecting to NAc and to basolateral amygdale (BLA). Furthermore, we demonstrate that D2 receptors enhance Kv7.4 currents through Gi/o protein and redox-dependent cellular pathway. Finally, we show this D2 mediated auto-inhibition is blunted in a social defeat mice model of depression, a phenomenon that may contribute to the altered excitability of VTA DA neurons in depressed animals. These results provide a new perspective for understanding the molecular mechanism of the excitability of VTA DA neurons and for potential new strategies against mental disorders involving altered excitability of DA neurons, such as major depression and drug addictions. |
| first_indexed | 2024-12-11T07:26:33Z |
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| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-11T07:26:33Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-674c1bcd84634482bac1952e3c6e64cd2022-12-22T01:15:56ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-12-011310.3389/fncel.2019.00557488447Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental AreaMin Su0Min Su1Min Su2Li Li3Li Li4Li Li5Jing Wang6Jing Wang7Jing Wang8Jing Wang9Hui Sun10Hui Sun11Hui Sun12Ludi Zhang13Ludi Zhang14Ludi Zhang15Chen Zhao16Chen Zhao17Chen Zhao18Ying Xie19Nikita Gamper20Nikita Gamper21Nikita Gamper22Nikita Gamper23Xiaona Du24Xiaona Du25Xiaona Du26Hailin Zhang27Hailin Zhang28Hailin Zhang29Department of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaDepartment of Pharmacochemistry, Hebei University of Chinese Medicine, Shijiazhuang, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaCenter for the Experimental Animal, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaFaculty of Biological Sciences, University of Leeds, Leeds, United KingdomDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, ChinaThe Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, ChinaDopaminergic neurons in the ventral tegmental area (VTA) encode behavioral patterns important in reward and drug addiction as well as in emotional disorders. These functions of dopamine neurons are directly related to the release of dopamine in the targeted regions of the brain which are, thus, controlled by the excitability of dopamine neurons. One mechanism for modulation of dopamine neuronal excitability is mediated by the auto dopamine type 2 (D2) receptors, through activation of a Kir3/GIRK K+ channel which inhibits the firing of dopamine neurons. In this study, we provide evidence that Kv7.4, in addition to Kir3.2 channels, contributes to dopamine (DA)-mediated auto-inhibition of DA activity projecting to NAc and to basolateral amygdale (BLA). Furthermore, we demonstrate that D2 receptors enhance Kv7.4 currents through Gi/o protein and redox-dependent cellular pathway. Finally, we show this D2 mediated auto-inhibition is blunted in a social defeat mice model of depression, a phenomenon that may contribute to the altered excitability of VTA DA neurons in depressed animals. These results provide a new perspective for understanding the molecular mechanism of the excitability of VTA DA neurons and for potential new strategies against mental disorders involving altered excitability of DA neurons, such as major depression and drug addictions.https://www.frontiersin.org/article/10.3389/fncel.2019.00557/fullKv7/M channelsKir3/GIRK channelventral tegmental areadopamine neuronD2 receptorcircuit |
| spellingShingle | Min Su Min Su Min Su Li Li Li Li Li Li Jing Wang Jing Wang Jing Wang Jing Wang Hui Sun Hui Sun Hui Sun Ludi Zhang Ludi Zhang Ludi Zhang Chen Zhao Chen Zhao Chen Zhao Ying Xie Nikita Gamper Nikita Gamper Nikita Gamper Nikita Gamper Xiaona Du Xiaona Du Xiaona Du Hailin Zhang Hailin Zhang Hailin Zhang Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area Frontiers in Cellular Neuroscience Kv7/M channels Kir3/GIRK channel ventral tegmental area dopamine neuron D2 receptor circuit |
| title | Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area |
| title_full | Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area |
| title_fullStr | Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area |
| title_full_unstemmed | Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area |
| title_short | Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area |
| title_sort | kv7 4 channel contribute to projection specific auto inhibition of dopamine neurons in the ventral tegmental area |
| topic | Kv7/M channels Kir3/GIRK channel ventral tegmental area dopamine neuron D2 receptor circuit |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00557/full |
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