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 

机构地区：[1]National Research Tomsk State University,Tomsk,Russia [2]Skolkovo Institute of Science and Technology,Moscow Region,Russia [3]University of Chicago,IL,USA [4]Siberian Medical University,Tomsk,Russia [5]M.V.Lomonosov Moscow State University,Moscow,Russia

出　　处：《Genes & Diseases》2015年第4期328-336,共9页基因与疾病（英文）

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).

摘　　要：During the last two decadesnumerous research teams demonstratedthat skeletalmuscles function as an exercise-dependent endocrine organ secreting dozens of myokines.Variety of physiological and pathophysiological implications of skeletalmusclemyokines secretion has been described;however,upstream signals and sensing mechanisms underlying this phenomenon remain poorly understood.It 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 channels.Recently,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 chelators.These data allowed us to suggest a novel[Nat]i/[Kt]i-sensitive,Ca2t i-independent mechanism of excitation-transcription coupling which triggers myokine production.This 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.

关 键 词：MYOKINES SECRETION Skeletal muscle TRANSCRIPTION Translation 

分 类 号：TP3[自动化与计算机技术—计算机科学与技术]