{"title":"GIRK通道活性的氧化还原约束。","authors":"Anna Boccaccio, Rocio K Finol-Urdaneta","doi":"10.1093/function/zqad027","DOIUrl":null,"url":null,"abstract":"pr otein-gated inw ardl y r ectifying potassium (GIRK, Kir3.x) hannels belong to the large family of inw ardl y r ectifying potasium (Kir) channels expressed throughout the body. Activation nd consequent opening of GIRK channels allow inward flow of otassium (K + ) ions into the cell resulting in membrane potenial hyperpolarization and decr eased excita bility. Thus, GIRK hannels play a key role in regulating the activity of neurons and ontrolling important physiological processes including neuonal excita bility, heart r ate , and pain per ception. 1 GIRK channels are integral membrane proteins, existing s homoor heterotetr amers. Eac h monomer features two embrane-spanning helices (M1 and M2), a re-entrant P-loop or controlling ion permeation and selectivity, and extensive ntracellular aminoand carboxy-termini crucial for channel ating. Permeation is regulated by an inner helix gate formed y the M2 segments and a cytoplasmic G-loop gate. 1 Acti v ation of GIRK channels is mediated by the direct interction of G βγ subunits, released from various G protein-coupled ece ptors (GPCRs) upon the acti v ation of inhibitory neuroransmitter r ece ptors. Howev er, the acti vity of GIRK channels epends on the presence of the membrane anionic phospholipid hosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 or PIP 2 ) while it s also modulated by ubiquitously present sodium (Na + ) ions. urthermore , GIRK c hannels ar e too r e gulated by c holesterol, hosphorylation, ethanol, etcetera. 1 The crystal structures of ecombinant GIRK channels have offered valuable insights into ow they are functionally regulated by various ligands. Thus, hannel opening is facilitated by PIP 2 at the plasma membrane, hereas G βγ and Na + modulate the c hannel’s inter action with IP 2 through conformational changes that govern the gating proess. 2 The intracellular milieu is a reducing environment charcterized by a balanced redox state. This state is crucial to upport cellular processes while serving as a pr otecti v e shield","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278978/pdf/","citationCount":"0","resultStr":"{\"title\":\"Redox Bridling of GIRK Channel Activity.\",\"authors\":\"Anna Boccaccio, Rocio K Finol-Urdaneta\",\"doi\":\"10.1093/function/zqad027\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"pr otein-gated inw ardl y r ectifying potassium (GIRK, Kir3.x) hannels belong to the large family of inw ardl y r ectifying potasium (Kir) channels expressed throughout the body. Activation nd consequent opening of GIRK channels allow inward flow of otassium (K + ) ions into the cell resulting in membrane potenial hyperpolarization and decr eased excita bility. Thus, GIRK hannels play a key role in regulating the activity of neurons and ontrolling important physiological processes including neuonal excita bility, heart r ate , and pain per ception. 1 GIRK channels are integral membrane proteins, existing s homoor heterotetr amers. Eac h monomer features two embrane-spanning helices (M1 and M2), a re-entrant P-loop or controlling ion permeation and selectivity, and extensive ntracellular aminoand carboxy-termini crucial for channel ating. Permeation is regulated by an inner helix gate formed y the M2 segments and a cytoplasmic G-loop gate. 1 Acti v ation of GIRK channels is mediated by the direct interction of G βγ subunits, released from various G protein-coupled ece ptors (GPCRs) upon the acti v ation of inhibitory neuroransmitter r ece ptors. Howev er, the acti vity of GIRK channels epends on the presence of the membrane anionic phospholipid hosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 or PIP 2 ) while it s also modulated by ubiquitously present sodium (Na + ) ions. urthermore , GIRK c hannels ar e too r e gulated by c holesterol, hosphorylation, ethanol, etcetera. 1 The crystal structures of ecombinant GIRK channels have offered valuable insights into ow they are functionally regulated by various ligands. Thus, hannel opening is facilitated by PIP 2 at the plasma membrane, hereas G βγ and Na + modulate the c hannel’s inter action with IP 2 through conformational changes that govern the gating proess. 2 The intracellular milieu is a reducing environment charcterized by a balanced redox state. This state is crucial to upport cellular processes while serving as a pr otecti v e shield\",\"PeriodicalId\":73119,\"journal\":{\"name\":\"Function (Oxford, England)\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278978/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Function (Oxford, England)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/function/zqad027\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Function (Oxford, England)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/function/zqad027","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
pr otein-gated inw ardl y r ectifying potassium (GIRK, Kir3.x) hannels belong to the large family of inw ardl y r ectifying potasium (Kir) channels expressed throughout the body. Activation nd consequent opening of GIRK channels allow inward flow of otassium (K + ) ions into the cell resulting in membrane potenial hyperpolarization and decr eased excita bility. Thus, GIRK hannels play a key role in regulating the activity of neurons and ontrolling important physiological processes including neuonal excita bility, heart r ate , and pain per ception. 1 GIRK channels are integral membrane proteins, existing s homoor heterotetr amers. Eac h monomer features two embrane-spanning helices (M1 and M2), a re-entrant P-loop or controlling ion permeation and selectivity, and extensive ntracellular aminoand carboxy-termini crucial for channel ating. Permeation is regulated by an inner helix gate formed y the M2 segments and a cytoplasmic G-loop gate. 1 Acti v ation of GIRK channels is mediated by the direct interction of G βγ subunits, released from various G protein-coupled ece ptors (GPCRs) upon the acti v ation of inhibitory neuroransmitter r ece ptors. Howev er, the acti vity of GIRK channels epends on the presence of the membrane anionic phospholipid hosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 or PIP 2 ) while it s also modulated by ubiquitously present sodium (Na + ) ions. urthermore , GIRK c hannels ar e too r e gulated by c holesterol, hosphorylation, ethanol, etcetera. 1 The crystal structures of ecombinant GIRK channels have offered valuable insights into ow they are functionally regulated by various ligands. Thus, hannel opening is facilitated by PIP 2 at the plasma membrane, hereas G βγ and Na + modulate the c hannel’s inter action with IP 2 through conformational changes that govern the gating proess. 2 The intracellular milieu is a reducing environment charcterized by a balanced redox state. This state is crucial to upport cellular processes while serving as a pr otecti v e shield