Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: UNIPROT:P21817 (
RyR1
)
1,154
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In this study, we tested the hypothesis that
RyR1
Ca2+ channel closure is sensitive to outward trans-SR membrane Ca2+ gradients established by SERCA1 pumping. To perform these studies we employed stopped-flow rapid-kinetic fluorescence methods to measure and assess how variation in trans-SR membrane Ca2+ distribution affects evolution of
RyR1
Ca2+ leaks in
RyR1
/CASQ1/SERCA1-rich HSR vesicles. Our studies showed that rapid filling of a Mag-Fura-2-sensitive free Ca2+ pool during SERCA1-mediated Ca2+ sequestration appears to be a crucial condition allowing
RyR1
Ca2+ channels to close once reloading of luminal Ca2+ stores is complete. Disruption in the filling of this pool caused activation of ruthenium red-inhibitable
RyR1
Ca2+ leaks suggesting that SERCA1 pump formation of outward Ca2+ gradients is an important aspect of Ca2+ flux control channel opening and closing. In addition, our observed ryanodine-induced shift in luminal Ca2+ from free to a
CTC
.Ca+-sensitive, CASQ1-associated bound compartment, underscores the complex organization and regulation of luminal Ca2+. Our study provides, strong evidence that
RyR1
functional states directly and indirectly influence the compartmentation of luminal Ca2+. This, in turn, is influenced by the activity of SERCA1 pumps to both fill luminal pools while synchronously reducing Ca2+ levels on the cytosolic face of
RyR1
channels.
...
PMID:Luminal Ca<sup>2+</sup> Regulation of RyR1 Ca<sup>2+</sup> Channel Leak Activation and Inactivation in Sarcoplasmic Reticulum Membrane Vesicles. 3316 53
