Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation

Konig, Stéphane; Hinard, Valérie; Arnaudeau, Serge; Holzer, Nicolas; Potter, Gael; Bader, Charles; Bernheim, Laurent

doi:10.1074/jbc.M313932200

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Title		Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation
Authors		Konig, Stéphane Hinard, Valérie Arnaudeau, Serge Holzer, Nicolas Potter, Gael Bader, Charles Bernheim, Laurent
Published in		Journal of Biological Chemistry. 2004, vol. 279, no. 27, p. 28187-28196
Abstract		It is widely thought that myogenin is one of the earliest detectable markers of skeletal muscle differentiation. Here we show that, during human myoblast differentiation, an inward rectifier K(+) channel (Kir2.1) and its associated hyperpolarization trigger expression and activity of the myogenic transcription factors, myogenin and myocyte enhancer factor-2 (MEF2). Furthermore, Kir2.1 current precedes and is required for the developmental increase in expression/activity of myogenin and MEF2. Drugs or antisense reducing Kir2.1 current diminished or suppressed fusion as well as expression/activity of myogenin and MEF2. In contrast, LY294002, an inhibitor of phosphatidylinositol 3-kinase (a pathway controlling initiation of the myogenic program) that inhibited both myogenin/MEF2 expression and fusion, did not affect Kir2.1 current. This non-blockade by LY294002 indicates that Kir2.1 acts upstream of myogenin and MEF2. We propose that Kir2.1 channel activation is a required key early event that initiates myogenesis by turning on myogenin and MEF2 transcription factors via a hyperpolarization-activated Ca(2+)-dependent pathway.
Keywords		Blotting, Western — Calcium/metabolism — Calibration — Cell Differentiation — Cell Division — Cell Membrane/ metabolism — Cells, Cultured — Chromones/pharmacology — DNA-Binding Proteins/ biosynthesis — Electrophysiology — Genes, Reporter — Humans — Immunohistochemistry — Ions — Kinetics — Membrane Potentials — Microscopy, Confocal — Microscopy, Fluorescence — Morpholines/pharmacology — Myoblasts/ metabolism — Myogenic Regulatory Factors — Myogenin/ biosynthesis — Oligonucleotides, Antisense/metabolism — Potassium Channels, Inwardly Rectifying/metabolism — Time Factors — Transcription Factors/ biosynthesis — Transcription, Genetic — Transfection
Identifiers		DOI: 10.1074/jbc.M313932200 PMID: 15084602
Full text		Article - Limited access to UNIGE Other version: http://www.jbc.org/content/279/27/28187.full.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales
Citation (ISO format)		KONIG, Stéphane et al. Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation. In: Journal of Biological Chemistry, 2004, vol. 279, n° 27, p. 28187-28196. doi: 10.1074/jbc.M313932200 https://archive-ouverte.unige.ch/unige:10324