title: The potassium channels TASK2 and TREK1 regulate functional differentiation of murine skeletal muscle cells.
abstract: Two-pore domain potassium (K2P) channels influence basic cellular parameters such as resting membrane potential, cellular excitability, or intracellular Ca2+-concentration [Ca2+]iWhile the physiological importance of K2Pchannels in different organ systems (e.g., heart, central nervous system, or immune system) has become increasingly clear over the last decade, their expression profile and functional role in skeletal muscle cells (SkMC) remain largely unknown. The mouse SkMC cell line C2C12, wild-type mouse muscle tissue, and primary mouse muscle cells (PMMs) were analyzed using quantitative PCR, Western blotting, and immunohistochemical stainings as well as functional analysis including patch-clamp measurements and Ca2+imaging. Mouse SkMC express TWIK-related acid-sensitive K+channel (TASK) 2, TWIK-related K+channel (TREK) 1, TREK2, and TWIK-related arachidonic acid stimulated K+channel (TRAAK). Except TASK2 all mentioned channels were upregulated in vitro during differentiation from myoblasts to myotubes. TASK2 and TREK1 were also functionally expressed and upregulated in PMMs isolated from mouse muscle tissue. Inhibition of TASK2 and TREK1 during differentiation revealed a morphological impairment of myoblast fusion accompanied by a downregulation of maturation markers. TASK2 and TREK1 blockade led to a decreased K+outward current and a decrease of ACh-dependent Ca2+influx in C2C12 cells as potential underlying mechanisms. K2P-channel expression was also detected in human muscle tissue by immunohistochemistry pointing towards possible relevance for human muscle cell maturation and function. In conclusion, our findings for the first time demonstrate the functional expression of TASK2 and TREK1 in muscle cells with implications for differentiation processes warranting further investigations in physiologic and pathophysiologic scenarios.
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Ali M
authors.identifier: http://orcid.org/0000-0003-4454-6542
authors.initials: AM
authors.lastname: Afzali
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany; tobias.ruck@ukmuenster.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ruck
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Herrmann
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Janette
authors.initials: J
authors.lastname: Iking
authors.affiliation: Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.affiliation: Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Preuβe
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Stenzel
authors.affiliation: Institute of Physiology I, University of Münster, Münster, Germany; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bittner
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C498739:Kcnk5 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D011188:Potassium
keywords: C2C12; K2P channels; TASK2; TREK1; calcium imaging; differentiation; muscle cells; myogenesis; patch clamp