Skeletal muscle as an endocrine organ:Role of[Na+]i/[K+]i-mediated excitation-transcription coupling

作     者：Leonid V.Kapilevich Tatyana A.Kironenko Anna N.Zaharova Yuri V.Kotelevtsev Nickolai O.Dulin Sergei N.Orlov 

作者机构：National Research Tomsk State UniversityTomskRussia Skolkovo Institute of Science and TechnologyMoscow RegionRussia University of ChicagoILUSA Siberian Medical UniversityTomskRussia M.V.Lomonosov Moscow State UniversityMoscowRussia 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2015年第2卷第4期

页      面：328-336页

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 08[工学] 0703[理学-化学] 0812[工学-计算机科学与技术（可授工学、理学学位）] 

基　　金：This work was supported by grants from the Canadian Institutes for Health Research(MOP-81392) the Kidney Foundation of Canada,the Heart and Stroke Foundation of Canada,Russian Foundation for Fundamental Research(15-04-00101) the Russian Scientific Foundation(14-15-00006) Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000430(N.O.D) 

主　　题：Myokines Secretion Skeletal muscle Transcription Translation 

摘      要：During the last two decadesnumerous research teams demonstratedthat skeletalmuscles function as an exercise-dependent endocrine organ secreting dozens of *** of physiological and pathophysiological implications of skeletalmusclemyokines secretion has been described;however,upstream signals and sensing mechanisms underlying this phenomenon remain poorly *** is well documented that in skeletal muscles intensive exercise triggers dissipation of transmembrane gradient of monovalent cations caused by permanent activation of voltage-gated Nat and Kt ***,we demonstrated that sustained elevation of the[Nat]i/[Kt]i ratio triggers expression of dozens ubiquitous genes including several canonical myokines,such as interleukin-6 and cyclooxygenase 2,in the presence of intra-and extracellular Ca2t *** data allowed us to suggest a novel[Nat]i/[Kt]i-sensitive,Ca2t i-independent mechanism of excitation-transcription coupling which triggers myokine *** pathway exists in parallel with canonical signaling mediated by Ca2t i,AMP-activated protein kinase and hypoxia-inducible factor 1a(HIF-1a).In ourmini-reviewwe briefly summarize data supporting this hypothesis as well as unresolved issues aiming to forthcoming studies.