title: Type 1 inositol (1,4,5)-trisphosphate receptor activates ryanodine receptor 1 to mediate calcium spark signaling in adult mammalian skeletal muscle.
abstract: Functional coupling between inositol (1,4,5)-trisphosphate receptor (IP(3)R) and ryanodine receptor (RyR) represents a critical component of intracellular Ca(2+) signaling in many excitable cells; however, the role of this mechanism in skeletal muscle remains elusive. In skeletal muscle, RyR-mediated Ca(2+) sparks are suppressed in resting conditions, whereas application of transient osmotic stress can trigger activation of Ca(2+) sparks that are restricted to the periphery of the fiber. Here we show that onset of these spatially confined Ca(2+) sparks involves interaction between activation of IP(3)R and RyR near the sarcolemmal membrane. Pharmacological prevention of IP(3) production or inhibition of IP(3)R channel activity abolishes stress-induced Ca(2+) sparks in skeletal muscle. Although genetic ablation of the type 2 IP(3)R does not appear to affect Ca(2+) sparks in skeletal muscle, specific silencing of the type 1 IP(3)R leads to ablation of stress-induced Ca(2+) sparks. Our data indicate that membrane-delimited signaling involving cross-talk between IP(3)R1 and RyR1 contributes to Ca(2+) spark activation in skeletal muscle.
authors.affiliation: Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Andoria
authors.initials: A
authors.lastname: Tjondrokoesoemo
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Pei-Hui
authors.initials: PH
authors.lastname: Lin
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ferrante
authors.forename: Natalia
authors.initials: N
authors.lastname: Shirokova
authors.forename: Marco
authors.initials: M
authors.lastname: Brotto
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D005786:Gene Expression Regulation; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D008957:Models, Genetic; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009995:Osmosis; D018408:Patch-Clamp Techniques; D010957:Plasmids / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D034741:RNA, Small Interfering; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium