The LRRC8/VRAC anion channel facilitates myogenic differentiation of murine myoblasts by promoting membrane hyperpolarization

The Journal of Biological Chemistry
Lingye ChenTobias Stauber

Abstract

Skeletal muscle myoblast differentiation involves elaborate signaling networks, including the activity of various ion channels and transporters. Several K+ and Ca2+ channels have been shown to affect myogenesis, but little is known about roles of Cl- channels in the associated processes. Here, we report that the leucine-rich repeat containing family 8 (LRRC8)/volume-regulated anion channel (VRAC) promotes mouse myoblast differentiation. All LRRC8 subunits of heteromeric VRAC were expressed during myotube formation of murine C2C12 myoblasts. Pharmacological VRAC inhibitors, siRNA-mediated knockdown of the essential VRAC subunit LRRC8A, or VRAC activity-suppressing overexpression of LRRC8A effectively reduced the expression of the myogenic transcription factor myogenin and suppressed myoblast fusion while not affecting myoblast proliferation. We found that inhibiting VRAC impairs plasma membrane hyperpolarization early during differentiation. At later times (more than 6 h after inducing differentiation), VRAC inhibition no longer suppressed myoblast differentiation, suggesting that VRAC acts upstream of K+ channel activation. Consequently, VRAC inhibition prevented the increase of intracellular steady-state Ca2+ levels that norma...Continue Reading

References

Sep 1, 1989·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·R J PrzybylskiA C Kirby
Feb 1, 1997·The American Journal of Physiology·T VoetsB Nilius
Dec 6, 1997·Current Opinion in Genetics & Development·K Walsh, H Perlman
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·P BijlengaL Bernheim
May 16, 2001·The Journal of Cell Biology·J Fischer-LougheedL Bernheim
Jun 11, 2002·American Journal of Physiology. Cell Physiology·Iris CartonJan Eggermont
Dec 18, 2008·The Journal of Biological Chemistry·Basile DarbellayLaurent Bernheim
Jun 30, 2009·Stem Cell Reviews and Reports·Sarah SundelacruzDavid L Kaplan
Jan 26, 2010·Current Opinion in Clinical Nutrition and Metabolic Care·Jong-Sun Kang, Robert S Krauss
Feb 19, 2010·American Journal of Physiology. Cell Physiology·Iva NeveuxMaria L Valencik
Feb 4, 2012·Cold Spring Harbor Perspectives in Biology·C Florian BentzingerMichael A Rudnicki
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Apr 25, 2013·Science Signaling·Sajedah M HindiAshok Kumar
Jul 25, 2013·Frontiers in Physiology·Ming Yang, William J Brackenbury
Apr 23, 2014·The Journal of Experimental Medicine·Lalit KumarRaif S Geha
Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Fabio A IannottiVincenzo Di Marzo
Sep 11, 2014·Human Molecular Genetics·Sonia SaccoSaïd Bendahhou
Feb 14, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Keiko NakanishiNobuhiro Morishima
Dec 2, 2015·Pflügers Archiv : European journal of physiology·Alexander A Mongin
Jan 8, 2016·Pflügers Archiv : European journal of physiology·Stine F PedersenBernd Nilius
Apr 2, 2016·Nature Reviews. Molecular Cell Biology·Thomas J Jentsch
Aug 5, 2016·American Journal of Physiology. Cell Physiology·Ali M AfzaliSven G Meuth
Apr 19, 2017·Scientific Reports·Shintaro MandaiShinichi Uchida
Apr 25, 2017·Nature Cell Biology·Yanhui ZhangRajan Sah
Jun 18, 2017·Frontiers in Pharmacology·Jonas FriardIsabelle Rubera
Jan 27, 2018·Nature Communications·Chen KangRajan Sah
May 19, 2018·Nature Communications·Till StuhlmannThomas J Jentsch

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Mar 3, 2021·Annual Review of Biophysics·Julia R Lazzari-DeanEvan W Miller
Sep 2, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Corinne S WilsonAlexander A Mongin

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