title: β-Adrenergic inhibition of contractility in L6 skeletal muscle cells.
abstract: The β-adrenoceptors (β-ARs) control many cellular processes. Here, we show that β-ARs inhibit calcium depletion-induced cell contractility and subsequent cell detachment of L6 skeletal muscle cells. The mechanism underlying the cell detachment inhibition was studied by using a quantitative cell detachment assay. We demonstrate that cell detachment induced by depletion of extracellular calcium is due to myosin- and ROCK-dependent contractility. The β-AR inhibition of L6 skeletal muscle cell detachment was shown to be mediated by the β(2)-AR and increased cAMP but was surprisingly not dependent on the classical downstream effectors PKA or Epac, nor was it dependent on PKG, PI3K or PKC. However, inhibition of potassium channels blocks the β(2)-AR mediated effects. Furthermore, activation of potassium channels fully mimicked the results of β(2)-AR activation. In conclusion, we present a novel finding that β(2)-AR signaling inhibits contractility and thus cell detachment in L6 skeletal muscle cells by a cAMP and potassium channel dependent mechanism.
authors.affiliation: Department of Physiology, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Anette I
authors.initials: AI
authors.lastname: Öberg
authors.forename: Nodi
authors.initials: N
authors.lastname: Dehvari
authors.forename: Tore
authors.initials: T
authors.lastname: Bengtsson
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004917:Erythromycin / Q000031:analogs & derivatives / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D015221:Potassium Channels; D018343:Receptors, Adrenergic, beta-2; D004917:Erythromycin; C057513:erythromycin propionate-N-acetylcysteinate; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D054460:rho-Associated Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium; D000111:Acetylcysteine