The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels
Introduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1–TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1330167/full |
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| author | Yating An Jingyi Hu Han Hao Weixin Zhao Xiaoxue Zhang Jicheng Shao Caixue Wang Xinmeng Li Chao Liu Jinsha He Yiwen Zhao Hailin Zhang Xiaona Du |
| author_facet | Yating An Jingyi Hu Han Hao Weixin Zhao Xiaoxue Zhang Jicheng Shao Caixue Wang Xinmeng Li Chao Liu Jinsha He Yiwen Zhao Hailin Zhang Xiaona Du |
| author_sort | Yating An |
| collection | DOAJ |
| description | Introduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1–TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia verruciformis, and predispose individuals to human papilloma virus. However, the impact of TMC on peripheral sensation pain has not been previously investigated.Methods: RNAscope was employed to detect the distribution of TMC6 mRNA in DRG neurons. Electrophysiological recordings were conducted to investigate the effects of TMC6 on neuronal characteristics and M channel activity. Zn2+ indicators were utilized to detect the zinc concentration in DRG tissues and dissociated neurons. A series of behavioural tests were performed to assess thermal and mechanical sensation in mice under both physiological and pathological conditions.Results and Discussion: We demonstrated that TMC6 is mainly expressed in small and medium dorsal root ganglion (DRG) neurons and is involved in peripheral heat nociception. Deletion of TMC6 in DRG neurons hyperpolarizes the resting membrane potential and inhibits neuronal excitability. Additionally, the function of the M channel is enhanced in TMC6 deletion DRG neurons owing to the increased quantity of free zinc in neurons. Indeed, heat and mechanical hyperalgesia in chronic pain are alleviated in TMC6 knockout mice, particularly in the case of heat hyperalgesia. This suggests that TMC6 in the small and medium DRG neurons may be a potential target for chronic pain treatment. |
| first_indexed | 2024-03-07T23:50:58Z |
| format | Article |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-07T23:50:58Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-4b46dc61205b4c78b8f3d0461fa1c5a62024-02-19T04:49:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-02-011510.3389/fphar.2024.13301671330167The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channelsYating An0Jingyi Hu1Han Hao2Weixin Zhao3Xiaoxue Zhang4Jicheng Shao5Caixue Wang6Xinmeng Li7Chao Liu8Jinsha He9Yiwen Zhao10Hailin Zhang11Xiaona Du12Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaThe Forth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaThe Key Laboratory of Experimental Animal, Department of Animal Care, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, Hebei, ChinaIntroduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1–TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia verruciformis, and predispose individuals to human papilloma virus. However, the impact of TMC on peripheral sensation pain has not been previously investigated.Methods: RNAscope was employed to detect the distribution of TMC6 mRNA in DRG neurons. Electrophysiological recordings were conducted to investigate the effects of TMC6 on neuronal characteristics and M channel activity. Zn2+ indicators were utilized to detect the zinc concentration in DRG tissues and dissociated neurons. A series of behavioural tests were performed to assess thermal and mechanical sensation in mice under both physiological and pathological conditions.Results and Discussion: We demonstrated that TMC6 is mainly expressed in small and medium dorsal root ganglion (DRG) neurons and is involved in peripheral heat nociception. Deletion of TMC6 in DRG neurons hyperpolarizes the resting membrane potential and inhibits neuronal excitability. Additionally, the function of the M channel is enhanced in TMC6 deletion DRG neurons owing to the increased quantity of free zinc in neurons. Indeed, heat and mechanical hyperalgesia in chronic pain are alleviated in TMC6 knockout mice, particularly in the case of heat hyperalgesia. This suggests that TMC6 in the small and medium DRG neurons may be a potential target for chronic pain treatment.https://www.frontiersin.org/articles/10.3389/fphar.2024.1330167/fulldorsal root ganglionTMC6M channelheat hyperalgesiachronic pain |
| spellingShingle | Yating An Jingyi Hu Han Hao Weixin Zhao Xiaoxue Zhang Jicheng Shao Caixue Wang Xinmeng Li Chao Liu Jinsha He Yiwen Zhao Hailin Zhang Xiaona Du The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels Frontiers in Pharmacology dorsal root ganglion TMC6 M channel heat hyperalgesia chronic pain |
| title | The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels |
| title_full | The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels |
| title_fullStr | The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels |
| title_full_unstemmed | The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels |
| title_short | The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels |
| title_sort | transmembrane channel like 6 tmc6 in primary sensory neurons involving thermal sensation via modulating m channels |
| topic | dorsal root ganglion TMC6 M channel heat hyperalgesia chronic pain |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1330167/full |
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