title: Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation.
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.
authors.affiliation: Département de Physiologie, Centre Médical Universitaire, Hôpital Cantonal Universitaire, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland. Stephane.Konig@medecine.unige.ch
authors.forename: Stéphane
authors.initials: S
authors.lastname: Konig
authors.forename: Valérie
authors.initials: V
authors.lastname: Hinard
authors.forename: Serge
authors.initials: S
authors.lastname: Arnaudeau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Holzer
authors.forename: Gaël
authors.initials: G
authors.lastname: Potter
authors.forename: Charles R
authors.initials: CR
authors.lastname: Bader
authors.forename: Laurent
authors.initials: L
authors.lastname: Bernheim
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002138:Calibration; D002454:Cell Differentiation; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004594:Electrophysiology; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D007477:Ions; D007700:Kinetics; D064326:MEF2 Transcription Factors; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology; D032446:Myoblasts / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D018008:Myogenin / Q000096:biosynthesis*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D002867:Chromones; D004268:DNA-Binding Proteins; D007477:Ions; D064326:MEF2 Transcription Factors; C503799:MYOG protein, human; D009025:Morpholines; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D016376:Oligonucleotides, Antisense; D000081082:Phosphoinositide-3 Kinase Inhibitors; D024661:Potassium Channels, Inwardly Rectifying; D014157:Transcription Factors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D002118:Calcium