个体化治疗依赖 K 的病理。
Personalized Therapeutics for K-Dependent Pathologies.
机构信息
Center for the Investigation of Membrane Excitability Diseases and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA; email:
出版信息
Annu Rev Pharmacol Toxicol. 2023 Jan 20;63:541-563. doi: 10.1146/annurev-pharmtox-051921-123023. Epub 2022 Sep 28.
Abstract
Ubiquitously expressed throughout the body, ATP-sensitive potassium (K) 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 channel physiology, pathology, and pharmacology and considers the potential for more specific or effective therapeutic agents.
摘要
在体内广泛表达的 ATP 敏感性钾 (K) 通道将细胞代谢与多种组织中的电活动偶联；它们作为四个 Kir6 孔形成亚基和四个磺酰脲受体 (SUR) 亚基的独特组装导致了大量选择性通道开放剂和抑制剂药物。这些通道的功能获得或功能丧失突变导致的单基因病理学的范围，以及对这些病理学进行治疗纠正的可能性，现在已经很清楚。然而，虽然现有药物可以有效治疗特定的病理学，但与其他 Kir6 或 SUR 亚家族成员的交叉反应可能导致每种病理学的药物诱导版本，并可能限制治疗的有效性。这篇综述讨论了 K 通道生理学、病理学和药理学的背景，并考虑了更具特异性或更有效的治疗药物的可能性。
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