Zha Tingfeng, Fang Xinyi, Wan Jiamin, Chen Xiaoyan, Lin Jiu, Chen Qianming
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310006, China.
Biomolecules. 2025 Jan 23;15(2):165. doi: 10.3390/biom15020165.
Chronic pain and mental health disorders, such as depression and anxiety, frequently co-occur and share underlying mechanisms involving neuronal excitability and synaptic transmission. The inwardly rectifying potassium channel 4.1 (Kir4.1), predominantly expressed in glial cells, is crucial for maintaining extracellular potassium and glutamate homeostasis. Dysregulation of Kir4.1 leads to altered neuronal activity, contributing to both chronic pain and mental health disorders. In chronic pain, downregulation of Kir4.1 impairs potassium buffering and glutamate clearance, increasing neuronal excitability and enhancing pain signaling through peripheral and central sensitization. In mental health disorders, impaired Kir4.1 function disrupts neurotrophic factor secretion and neuroinflammatory pathways, leading to mood disturbances. This review primarily summarizes findings from preclinical studies to examine the relationship between Kir4.1 and the pathogenesis of chronic pain and mental health disorders, discussing its molecular structure, expression patterns, and functional roles. Furthermore, we explore therapeutic strategies targeting Kir4.1, including pharmacological modulators and gene therapy approaches, emphasizing its potential as a novel therapeutic target.
慢性疼痛与心理健康障碍，如抑郁症和焦虑症，经常同时出现，且共享涉及神经元兴奋性和突触传递的潜在机制。内向整流钾通道4.1（Kir4.1）主要在胶质细胞中表达，对维持细胞外钾和谷氨酸稳态至关重要。Kir4.1的失调会导致神经元活动改变，从而导致慢性疼痛和心理健康障碍。在慢性疼痛中，Kir4.1的下调会损害钾缓冲和谷氨酸清除，增加神经元兴奋性，并通过外周和中枢敏化增强疼痛信号。在心理健康障碍中，Kir4.1功能受损会破坏神经营养因子分泌和神经炎症途径，导致情绪障碍。本综述主要总结临床前研究的结果，以探讨Kir4.1与慢性疼痛和心理健康障碍发病机制之间的关系，讨论其分子结构、表达模式和功能作用。此外，我们还探索了针对Kir4.1的治疗策略，包括药理学调节剂和基因治疗方法，强调其作为新型治疗靶点的潜力。
