title: The maintenance ability and Ca2+availability of skeletal muscle are enhanced by sildenafil.
abstract: Sildenafil relaxes vascular smooth muscle cells and is used to treat pulmonary artery hypertension as well as erectile dysfunction. However, the effectiveness of sildenafil on skeletal muscle and the benefit of its clinical use have been controversial, and most studies focus primarily on tissues and organs from disease models without cellular examination. Here, the effects of sildenafil on skeletal muscle at the cellular level were examined using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca2+imaging experiments and cellular and biochemical studies. The proliferation of skeletal myoblasts was enhanced by sildenafil in a dose-independent manner. In skeletal myotubes, sildenafil enhanced the activity of ryanodine receptor 1, an internal Ca2+channel, and Ca2+movement that promotes skeletal muscle contraction, possibly due to an increase in the resting cytosolic Ca2+level and a unique microscopic shape in the myotube membranes. Therefore, these results suggest that the maintenance ability of skeletal muscle mass and the contractility of skeletal muscle could be improved by sildenafil by enhancing the proliferation of skeletal myoblasts and increasing the Ca2+availability of skeletal myotubes, respectively.
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Mei
authors.identifier: 0000-0003-0117-8604
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Keon Jin
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
authors.affiliation: School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Do Han
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002413:Cations, Divalent / Q000032:analysis / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002413:Cations, Divalent; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D002118:Calcium