title: Systemic ablation of RyR3 alters Ca2+ spark signaling in adult skeletal muscle.
abstract: Ca2+ sparks are localized intracellular Ca2+ release events from the sarcoplasmic reticulum in muscle cells that result from synchronized opening of ryanodine receptors (RyR). In mammalian skeletal muscle, RyR1 is the predominant isoform present in adult skeletal fibers, while some RyR3 is expressed during development. Functional studies have revealed a differential role for RyR1 and RyR3 in the overall Ca2+ signaling in skeletal muscle, but the contribution of these two isoforms to Ca2+ sparks in adult mammalian skeletal muscle has not been fully examined. When enzyme-disassociated, individual adult skeletal muscle fibers are exposed to an osmotic shock, the resting fiber converts from a quiescent to a highly active Ca2+ release state where Ca2+ sparks appear proximal to the sarcolemmal membrane. These osmotic shock-induced Ca2+ sparks occur in ryr3(-/-) muscle with a spatial distribution similar to that seen in wild type muscle. Kinetic analysis reveals that systemic ablation of RyR3 results in significant changes to the initiation, duration and amplitude of individual Ca2+ sparks in muscle fibers. These changes may reflect the adaptation of the muscle Ca2+ signaling or contractile machinery due to the loss of RyR3 expression in distal tissues, as biochemical assays identify significant changes in expression of myosin heavy chain protein in ryr3(-/-) muscle.
authors.affiliation: Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, United States.
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.forename: Christopher
authors.initials: C
authors.lastname: Ferrante
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirata
authors.forename: Claude
authors.initials: C
authors.lastname: Collet
authors.forename: Yi
authors.initials: Y
authors.lastname: Chu
authors.forename: Heping
authors.initials: H
authors.lastname: Cheng
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D009997:Osmotic Pressure; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D009218:Myosins; D002118:Calcium