Research Progress on HCN Channels in Neuropsychiatric Disorders

ZHOU Xiaohong^1,2#, WEI Siqi^1,2#, HAN Shuang^1,2#, LI Zicheng^1,3*

(¹Grade III Laboratory of Chinese Materia Medica Pharmacology Under the National Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China; ²College of Health Medicine, China Three Gorges University, Yichang 443002, China; ³College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China)

Abstract:

HCN channels (hyperpolarization-activated cyclic nucleotide-gated channels), members of the voltage-gated potassium channel superfamily, play pivotal roles in regulating cardiac pacing and neuronal excitability. These channels open under hyperpolarized membrane potentials, are permeable to sodium ions (Na⁺) and potassium ions (K⁺), and generate an inward current modulated by intracellular cAMP (cyclic adenosine monophosphate). Dysfunction of HCN channels has been implicated in various neurological disorders, including anxiety, depression, epilepsy, and Alzheimer’s disease. This review systematically summarizes the tissue distribution, structural features, physiological functions, and pathological contributions of HCN channels in neurological diseases, aiming to explore potential therapeutic strategies for neuropsychiatric disorders.

CSTR: 32200.14.cjcb.2025.08.0027