Laxation of skeletal muscle, sarcoplasmic endoplasmic reticulum Ca2+-ATPase 1a (SERCA1a) on the SR membrane uptakes cytosolic Ca2+ in to the SR to minimize the cytosolic Ca2+ level to that of the resting state and to refill the SR with Ca2+.two,6 An efficient arrangement of the proteins mentioned above is maintained by the specialized junctional membrane complicated (that may be, triad junction) where the 2-Methoxy-4-vinylphenol MedChemExpress t-tubule and SR membranes are closely juxtaposed.two,three,70 The triad junction supports the fast and frequent delivery and storage of Ca2+ into skeletal muscle. Junctophilin 1 (JP1), junctophilin two (JP2) and mitsugumin 29 (MG29) contribute to the formation and upkeep of the triad junction in skeletal muscle. Along with the feature of skeletal muscle contraction mentioned above, the value of Ca2+ entry from extracellular spaces to the cytosol in skeletal muscle has gained1 Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea; 2Department of Physiology, David Geffen College of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; 3Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Healthcare College, Boston, MA, USA and 4Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Correspondence: Professor EH Lee, Division of Physiology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea. E-mail: [email protected] Received 18 April 2017; revised 16 June 2017; accepted 28 JuneFunctional roles of extracellular Ca2+ entry inside the health and disease of skeletal muscle C-H Cho et alFigure 1 Ca2+ movements and associated proteins in skeletal muscle. (a) Proteins which might be connected to, or involved in, EC coupling, relaxation, ECCE, SOCE, integrin signaling, Tie2 signaling or TRPC-mediated extracellular Ca2+ entry in skeletal muscle are presented. Ang, angiopoietin; CSQ, calsequestrin; DHPR, dihydropyridine receptors; EC, excitation ontraction; ECCE, excitation-coupled Ca2+ entry; JP, junctophilin; MG, mitsugumin; RyR1, ryanodine receptor 1; SERCA1a, sarcoplasmicendoplasmic reticulum Ca2+-ATPase 1a; SOCE, storeoperated Ca2+ entry; SR, sarcoplasmic reticulum; STIM1, stromal interaction molecule 1; STIM1L, long kind of STIM1; Tie2 R, Tie2 receptor; TRPC, canonical-type transient receptor possible cation channels; t-tubule, transverse-tubule. (b) Directions with the signals are presented. Outside-in implies signals in the extracellular space or sarcolemmal (or t-tubule) membrane for the inside of cells such as cytosol, the SR membrane or the SR (arrows colored in red). Inside-out suggests the direction of outside-in signals in reverse (arrows colored in black). (c) The directions of Ca2+ movements throughout EC coupling, relaxation, ECCE, SOCE, integrin signaling, Tie2 signaling or TRPC-mediated extracellular Ca2+ entry in skeletal muscle are presented (dashed arrows).substantial interest over the past decade. In this review report, recent research on extracellular Ca2+ entry into skeletal muscle are reviewed together with descriptions in the proteins which can be related to, or that regulate, extracellular Ca2+ entry and their influences on skeletal muscle function and illness. EXTRACELLULAR CA2+ ENTRY INTO SKELETAL MUSCLE Orai1 and stromal interaction molecule 1-mediated SOCE in general Store-operated Ca2+ entry (SOCE) is amongst the modes of extracellular.