title: RyR3 amplifies RyR1-mediated Ca(2+)-induced Ca(2+) release in neonatal mammalian skeletal muscle.
abstract: The neonatal mammalian skeletal muscle contains both type 1 and type 3 ryanodine receptors (RyR1 and RyR3) located in the sarcoplasmic reticulum membrane. An allosteric interaction between RyR1 and dihydropyridine receptors located in the plasma membrane mediates voltage-induced Ca(2+) release (VICR) from the sarcoplasmic reticulum. RyR3, which disappears in adult muscle, is not involved in VICR, and the role of the transiently expressed RyR3 remains elusive. Here we demonstrate that RyR1 participates in both VICR and Ca(2+)-induced Ca(2+) release (CICR) and that RyR3 amplifies RyR1-mediated CICR in neonatal skeletal muscle. Confocal measurements of intracellular Ca(2+) in primary cultured mouse skeletal myotubes reveal active sites of Ca(2+) release caused by peripheral coupling between dihydropyridine receptors and RyR1. In myotubes lacking RyR3, the peripheral VICR component is unaffected, and RyR1s alone are able to support inward CICR propagation in most cells at an average speed of approximately 190 microm/s. With the co-presence of RyR1 and RyR3 in wild-type cells, unmitigated radial CICR propagates at 2,440 microm/s. Because neonatal skeletal muscle lacks a well developed transverse tubule system, the RyR3 reinforcement of CICR seems to ensure a robust, uniform, and synchronous activation of Ca(2+) release throughout the cell body. Such functional interplay between RyR1 and RyR3 can serve important roles in Ca(2+) signaling of cell differentiation and muscle contraction.
authors.affiliation: Laboratory of Cardiovascular Science, Gerontology Research Center, NIA National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: Z
authors.initials: Z
authors.lastname: Pan
authors.forename: H
authors.initials: H
authors.lastname: Takeshima
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: R Y
authors.initials: RY
authors.lastname: Nagaraj
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: H
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling; D002478:Cells, Cultured; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel