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Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A

(2017) JOURNAL OF PHYSIOLOGY-LONDON. 595(14). p.4769-4784
Author
Organization
Abstract
The type A trimeric intracellular cation channel (TRIC-A) is a major component of the nuclear and sarcoplasmic reticulum (SR) membranes of cardiac and skeletal muscle, and is localized closely with ryanodine receptor (RyR) channels in the SR terminal cisternae. The skeletal muscle of Tric-a knockout (KO) mice is characterized by Ca2+ overloaded and swollen SR and by changes in the properties of SR Ca2+ release. We therefore investigated whether RyR1 gating behaviour is modified in the SR from Tric-a KO mice by incorporating native RyR1 into planar phospholipid bilayers under voltage-clamp conditions. We find that RyR1 channels from Tric-a KO mice respond normally to cytosolic Ca2+, ATP, adenine, caffeine and to luminal Ca2+. However, the channels are more sensitive to the inactivating effects of divalent cations, thus, in the presence of Mg2+, ATP is inadequate as an activator. Additionally, channels are not characteristically activated by protein kinase A even though the phosphorylation levels of Ser2844 are similar to controls. The results of the present study suggest that TRIC-A functions as an excitatory modulator of RyR1 channels within the SR terminal cisternae. Importantly, this regulatory action of TRIC-A appears to be independent of (although additive to) any indirect consequences to RyR1 activity that arise as a result of K+ fluxes across the SR via TRIC-A.
Keywords
Ca2+ release, ryanodine receptor, sarcoplasmic reticulum, CARDIAC SARCOPLASMIC-RETICULUM, CALCIUM-RELEASE CHANNELS, RECESSIVE OSTEOGENESIS IMPERFECTA, DELETION MUTATION, MOUSE MODEL, CA2+, MODULATION, ACTIVATION, CONDUCTANCE, CAFFEINE

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MLA
El-Ajouz, Sam et al. “Dampened Activity of Ryanodine Receptor Channels in Mutant Skeletal Muscle Lacking TRIC-A.” JOURNAL OF PHYSIOLOGY-LONDON 595.14 (2017): 4769–4784. Print.
APA
El-Ajouz, S., Venturi, E., Witschas, K., Beech, M., Wilson, A. D., Lindsay, C., Eberhardt, D., et al. (2017). Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A. JOURNAL OF PHYSIOLOGY-LONDON, 595(14), 4769–4784.
Chicago author-date
El-Ajouz, Sam, Elisa Venturi, Katja Witschas, Matthew Beech, Abigail D Wilson, Chris Lindsay, David Eberhardt, et al. 2017. “Dampened Activity of Ryanodine Receptor Channels in Mutant Skeletal Muscle Lacking TRIC-A.” Journal of Physiology-london 595 (14): 4769–4784.
Chicago author-date (all authors)
El-Ajouz, Sam, Elisa Venturi, Katja Witschas, Matthew Beech, Abigail D Wilson, Chris Lindsay, David Eberhardt, Fiona O’Brien, Tsunaki Iida, Miyuki Nishi, Hiroshi Takeshima, and Rebecca Sitsapesan. 2017. “Dampened Activity of Ryanodine Receptor Channels in Mutant Skeletal Muscle Lacking TRIC-A.” Journal of Physiology-london 595 (14): 4769–4784.
Vancouver
1.
El-Ajouz S, Venturi E, Witschas K, Beech M, Wilson AD, Lindsay C, et al. Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A. JOURNAL OF PHYSIOLOGY-LONDON. 2017;595(14):4769–84.
IEEE
[1]
S. El-Ajouz et al., “Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A,” JOURNAL OF PHYSIOLOGY-LONDON, vol. 595, no. 14, pp. 4769–4784, 2017.
@article{8609519,
  abstract     = {The type A trimeric intracellular cation channel (TRIC-A) is a major component of the nuclear and sarcoplasmic reticulum (SR) membranes of cardiac and skeletal muscle, and is localized closely with ryanodine receptor (RyR) channels in the SR terminal cisternae. The skeletal muscle of Tric-a knockout (KO) mice is characterized by Ca2+ overloaded and swollen SR and by changes in the properties of SR Ca2+ release. We therefore investigated whether RyR1 gating behaviour is modified in the SR from Tric-a KO mice by incorporating native RyR1 into planar phospholipid bilayers under voltage-clamp conditions. We find that RyR1 channels from Tric-a KO mice respond normally to cytosolic Ca2+, ATP, adenine, caffeine and to luminal Ca2+. However, the channels are more sensitive to the inactivating effects of divalent cations, thus, in the presence of Mg2+, ATP is inadequate as an activator. Additionally, channels are not characteristically activated by protein kinase A even though the phosphorylation levels of Ser2844 are similar to controls. The results of the present study suggest that TRIC-A functions as an excitatory modulator of RyR1 channels within the SR terminal cisternae. Importantly, this regulatory action of TRIC-A appears to be independent of (although additive to) any indirect consequences to RyR1 activity that arise as a result of K+ fluxes across the SR via TRIC-A.},
  author       = {El-Ajouz, Sam and Venturi, Elisa and Witschas, Katja and Beech, Matthew and Wilson, Abigail D and Lindsay, Chris and Eberhardt, David and O'Brien, Fiona and Iida, Tsunaki and Nishi, Miyuki and Takeshima, Hiroshi and Sitsapesan, Rebecca},
  issn         = {0022-3751},
  journal      = {JOURNAL OF PHYSIOLOGY-LONDON},
  keywords     = {Ca2+ release,ryanodine receptor,sarcoplasmic reticulum,CARDIAC SARCOPLASMIC-RETICULUM,CALCIUM-RELEASE CHANNELS,RECESSIVE OSTEOGENESIS IMPERFECTA,DELETION MUTATION,MOUSE MODEL,CA2+,MODULATION,ACTIVATION,CONDUCTANCE,CAFFEINE},
  language     = {eng},
  number       = {14},
  pages        = {4769--4784},
  title        = {Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A},
  url          = {http://dx.doi.org/10.1113/jp273550},
  volume       = {595},
  year         = {2017},
}

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