Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200030, China.
National Center for Neurological Disorders, Shanghai, 200030, China.
Cell Mol Life Sci. 2024 Mar 13;81(1):135. doi: 10.1007/s00018-024-05163-w.
Parkinson's disease (PD) is a motor disorder resulting from dopaminergic neuron degeneration in the substantia nigra caused by age, genetics, and environment. The disease severely impacts a patient's quality of life and can even be life-threatening. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a member of the HCN1-4 gene family and is widely expressed in basal ganglia nuclei. The hyperpolarization-activated current mediated by the HCN channel has a distinct impact on neuronal excitability and rhythmic activity associated with PD pathogenesis, as it affects the firing activity, including both firing rate and firing pattern, of neurons in the basal ganglia nuclei. This review aims to comprehensively understand the characteristics of HCN channels by summarizing their regulatory role in neuronal firing activity of the basal ganglia nuclei. Furthermore, the distribution and characteristics of HCN channels in each nucleus of the basal ganglia group and their effect on PD symptoms through modulating neuronal electrical activity are discussed. Since the roles of the substantia nigra pars compacta and reticulata, as well as globus pallidus externus and internus, are distinct in the basal ganglia circuit, they are individually described. Lastly, this investigation briefly highlights that the HCN channel expressed on microglia plays a role in the pathological process of PD by affecting the neuroinflammatory response.
帕金森病(PD)是一种运动障碍,由年龄、遗传和环境引起的黑质多巴胺能神经元变性引起。该疾病严重影响患者的生活质量,甚至可能危及生命。超极化激活环核苷酸门控(HCN)通道是 HCN1-4 基因家族的成员,广泛表达于基底神经节核团。由 HCN 通道介导的超极化激活电流对与 PD 发病机制相关的神经元兴奋性和节律性活动具有显著影响,因为它会影响神经元的放电活动,包括基底神经节核团中神经元的放电率和放电模式。本综述旨在通过总结 HCN 通道在基底神经节核团神经元放电活动中的调节作用,全面了解 HCN 通道的特性。此外,还讨论了 HCN 通道在基底神经节核团各核团中的分布和特征,以及通过调节神经元电活动对 PD 症状的影响。由于黑质致密部和网状部以及苍白球外核和内核在基底神经节回路中的作用不同,因此分别进行了描述。最后,这项研究简要地强调了表达在小胶质细胞上的 HCN 通道通过影响神经炎症反应在 PD 的病理过程中发挥作用。