{"title":"Personalized Therapeutics for K<sub>ATP</sub>-Dependent Pathologies.","authors":"Colin G Nichols","doi":"10.1146/annurev-pharmtox-051921-123023","DOIUrl":null,"url":null,"abstract":"<p><p>Ubiquitously expressed throughout the body, ATP-sensitive potassium (K<sub>ATP</sub>) channels couple cellular metabolism to electrical activity in multiple tissues; their unique assembly as four Kir6 pore-forming subunits and four sulfonylurea receptor (SUR) subunits has resulted in a large armory of selective channel opener and inhibitor drugs. The spectrum of monogenic pathologies that result from gain- or loss-of-function mutations in these channels, and the potential for therapeutic correction of these pathologies, is now clear. However, while available drugs can be effective treatments for specific pathologies, cross-reactivity with the other Kir6 or SUR subfamily members can result in drug-induced versions of each pathology and may limit therapeutic usefulness. This review discusses the background to K<sub>ATP</sub> channel physiology, pathology, and pharmacology and considers the potential for more specific or effective therapeutic agents.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2000,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868118/pdf/nihms-1854017.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of pharmacology and toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-pharmtox-051921-123023","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Ubiquitously expressed throughout the body, ATP-sensitive potassium (KATP) channels couple cellular metabolism to electrical activity in multiple tissues; their unique assembly as four Kir6 pore-forming subunits and four sulfonylurea receptor (SUR) subunits has resulted in a large armory of selective channel opener and inhibitor drugs. The spectrum of monogenic pathologies that result from gain- or loss-of-function mutations in these channels, and the potential for therapeutic correction of these pathologies, is now clear. However, while available drugs can be effective treatments for specific pathologies, cross-reactivity with the other Kir6 or SUR subfamily members can result in drug-induced versions of each pathology and may limit therapeutic usefulness. This review discusses the background to KATP channel physiology, pathology, and pharmacology and considers the potential for more specific or effective therapeutic agents.
ATP 敏感性钾（KATP）通道在全身普遍表达，它将多种组织中的细胞新陈代谢与电活动结合在一起；这些通道由四个 Kir6 孔形成亚基和四个磺脲受体（SUR）亚基组成，其独特的组装方式催生了大量选择性通道开启剂和抑制剂药物。这些通道的功能增益突变或功能缺失突变导致的单基因病症的范围以及治疗纠正这些病症的潜力现在已经很清楚了。然而，虽然现有药物可以有效治疗特定病症，但与其他 Kir6 或 SUR 亚家族成员的交叉反应会导致药物诱导的各种病症，并可能限制治疗的有效性。这篇综述讨论了 KATP 通道生理学、病理学和药理学的背景，并探讨了更特异或更有效的治疗药物的潜力。
期刊介绍：
Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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