内向整流钾通道家族参与偏头痛发病机制的研究进展OA

Migraine is a neurovascular disorder and ranks as the second leading cause of disability worldwide.The Global Burden of Disease Study 2021 estimated that approximately 1.2 billion people are affected by migraine,making it one of the major contributors to years lived with disability years attributable to neurological disorders.The pathogenesis of migraine is complex and involves multiple processes,including activation of the trigeminovascular system,neuroinflammation,abnormal meningeal vasomotion,and central sensitization.Among these,potassium channels play a vital role in maintaining the resting membrane potential of cells,regulating neuronal excitability,modulating neurotransmitter release,and controlling vascular tone.In recent years,the inwardly rectifying potassium channel(Kir)family has become a hotspot in headache research.This family includes Kir2.x,G protein-coupled inwardly rectifying potassium channels(GIRK/Kir3.x),and ATP-sensitive potas-sium channels(KATP,Kir6.x/SUR),which are involved in membrane potential stabilization,receptor-coupled inhibition,spa-tial potassium buffering in glial cells,and metabolic-electrical activity coupling.Notably,the KATP channel opener levcromaka-lim can reliably induce migraine attacks in humans,making KATP channels one of the most translationally promising ion channel targets at present.This article focuses on the role of inwardly rectifying potassium channels in migraine,summarizes the distri-bution,mechanisms,and physiological functions of various Kir channels,and discusses the evidence supporting the involve-ment of the Kir family in migraine.Furthermore,it reviews the interactions among different Kir channels,as well as their cross-talk with canonical migraine pathways including CGRP,PACAP,and NO.Finally,it analyzes relevant therapeutic targets,current research limitations,and future directions.Overall,inwardly rectifying potassium channels are situated at critical nodes of functional coupling among neurons,glial cells,and vascular smooth muscle,representing an important entry point for under-standing migraine heterogeneity and developing precision therapeutics.