The W105G and W99G Sorcin Mutants Demonstrate the Role of the D Helix in the Ca2+-Dependent Interaction with Annexin VII and the Cardiac Ryanodine Receptor†

Biochemistry ◽  
2006 ◽  
Vol 45 (41) ◽  
pp. 12519-12529 ◽  
Author(s):  
Gianni Colotti ◽  
Carlotta Zamparelli ◽  
Daniela Verzili ◽  
Manuela Mella ◽  
Christopher M. Loughrey ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Dependent Interaction ◽  
Cardiac Ryanodine Receptor

scholarly journals The Role of Calsequestrin, Triadin, and Junctin in Conferring Cardiac Ryanodine Receptor Responsiveness to Luminal Calcium

2004 ◽  
Vol 86 (4) ◽  
pp. 2121-2128 ◽  
Author(s):  
Inna Györke ◽  
Nichole Hester ◽  
Larry R. Jones ◽  
Sandor Györke
Keyword(s):  
Ryanodine Receptor ◽  
Luminal Calcium ◽  
Cardiac Ryanodine Receptor

Role of calmodulin methionine residues in mediating productive association with cardiac ryanodine receptors

2006 ◽  
Vol 290 (2) ◽  
pp. H794-H799 ◽  
Author(s):  
Edward M. Balog ◽  
Laura E. Norton ◽  
David D. Thomas ◽  
Bradley R. Fruen
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Ryanodine Receptor ◽  
Ryanodine Receptors ◽  
Release Channel ◽  
Site Specific ◽  
High Affinity ◽  
Methionine Residues ◽  
Cardiac Ryanodine Receptor

Calmodulin (CaM) binds to the cardiac ryanodine receptor Ca2+ release channel (RyR2) with high affinity and may act as a regulatory channel subunit. Here we determine the role of CaM Met residues in the productive association of CaM with RyR2, as assessed via determinations of [3H]ryanodine and [35S]CaM binding to cardiac muscle sarcoplasmic reticulum (SR) vesicles. Oxidation of all nine CaM Met residues abolished the productive association of CaM with RyR2. Substitution of the COOH-terminal Mets of CaM with Leu decreased the extent of CaM inhibition of cardiac SR (CSR) vesicle [3H]ryanodine binding. In contrast, replacing the NH2-terminal Met of CaM with Leu increased the concentration of CaM required to inhibit CSR [3H]ryanodine binding but did not alter the extent of inhibition. Site-specific substitution of individual CaM Met residues with Gln demonstrated that Met124 was required for both high-affinity CaM binding to RyR2 and for maximal CaM inhibition. These results thus identify a Met residue critical for the productive association of CaM with RyR2 channels.

Role of Cys3602 in the function and regulation of the cardiac ryanodine receptor

2015 ◽  
Vol 467 (1) ◽  
pp. 177-190 ◽  
Author(s):  
Tao Mi ◽  
Zhichao Xiao ◽  
Wenting Guo ◽  
Yijun Tang ◽  
Florian Hiess ◽  
...  
Keyword(s):  
Binding Site ◽  
Ryanodine Receptor ◽  
Central Region ◽  
Calcium Release ◽  
Important Determinant ◽  
Cardiac Ryanodine Receptor

Cys3602 in cardiac ryanodine receptor (RyR) mediates the action of the thiol agent N-ethylmaleimide, but not 4,4′-dithiodipyridine (DTDP). A central region encompassing the calmodulin (CaM)-binding site and Cys3602 in cardiac RyR represents an important determinant of calcium-release activation and termination.

Role of cardiac ryanodine receptor calmodulin‐binding domains in mediating the action of arrhythmogenic calmodulin N‐domain mutation N54I

FEBS Journal ◽  
2019 ◽  
Vol 287 (11) ◽  
pp. 2256-2280 ◽  
Author(s):  
Mads T. Søndergaard ◽  
Yingjie Liu ◽  
Wenting Guo ◽  
Jinhong Wei ◽  
Ruiwu Wang ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Calmodulin Binding ◽  
Binding Domains ◽  
Cardiac Ryanodine Receptor

Abstract 5304: Dominant Negative Suppression of Rad Leads to Intracellular Ca 2+ Overload via Up-Regulation of Cardiac Ryanodine Receptor Activity

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mitsushige Murata ◽  
Hirotaka Yada ◽  
Hiroyuki Yamakawa ◽  
Yoshiyasu Aizawa ◽  
Shinsuke Yuasa ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Critical Role ◽  
Mean Amplitude ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Release Channel ◽  
Intracellular Ca ◽  
Mouse Cells ◽  
Cardiac Ryanodine Receptor

Background: We have recently reported that the ras-related small G-protein Rad plays a critical role in generating arrhythmias via regulation of L-type Ca 2+ channel. However, it has remained unclear whether or not the mechanism for its arrhythmogenesis is attributed only to L-type Ca 2+ channel activity. This study was designed to demonstrate the role of Rad in intracellular calcium homeostasis by cardiac-specific dominant negative suppression of Rad. Methods and results: Transgenic mice that overexpress dominant negative mutant Rad (DN Rad TG) driven by α-myosin heavy chain promoter were generated. To measure intracellular Ca 2+ concentration ([Ca 2+ ] i ), we recorded [Ca 2+ ] i transients and Ca 2+ sparks from isolated cardiomyocytes by confocal microscope. The mean amplitude of [Ca 2+ ] i transient was significantly increased in DN Rad TG cardiomyocytes, compared with WT littermate mouse cells (F/F 0 3.3 ± 0.2, n = 25, in DN Rad TG cells vs. 2.4 ± 0.1, n = 30, in WT cells, P<0.05). The frequency of Ca 2+ sparks was significantly higher in TG cells than in WT cells (5.2 ± 0.6 sparks•100 μm −1 •s −1 , n = 45 in TG cells vs. 1.9 ± 0.3 sparks•100 μm −1 •s −1 , n = 45, in WT controls, P<0.05), although there were no significant differences in their amplitudes. Furthermore, SR Ca 2+ content was not altered in TG cells, as assessed by caffeine-induced [Ca 2+ ] i transient. These results suggested that the properties of fundamental SR Ca 2+ release units might have been affected by the inhibition of endogenous Rad activity. To elucidate the mechanism for the increased frequency of SR Ca 2+ release channel, phosphorylation of Ser 2809 on cardiac ryanodine receptor (RYR2) was examined. The phosphorylation of RYR2 at Ser 2809 was significantly enhanced in TG mouse hearts compared with WT mice, implicating the upregulation of RYR2 activity in TG mice. Additionally, this Rad-mediated phosphorylation of RYR2 was regulated by protein kinase A (PKA) activity. Conclusions: Our results provided the first evidence that Rad regulated RYR2 activity via PKA signaling pathway. Thus, Rad might play a critical role in cellular Ca 2+ homeostasis via its inhibitory effects on RYR2 as well as L-type Ca 2+ channel.

Human Cardiac Ryanodine Receptor: Preparation, Crystallization and Preliminary X-ray Analysis of the N-terminal Region

2013 ◽  
Vol 20 (11) ◽  
pp. 1211-1216 ◽  
Author(s):  
L’ubomír Borko ◽  
Július Kostan ◽  
Alexandra Zahradníkova ◽  
Vladimír Pevala ◽  
Juraj Gasperík ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Terminal Region ◽  
X Ray ◽  
Cardiac Ryanodine Receptor

Antiarrhythmic Potential of Drugs Targeting the Cardiac Ryanodine Receptor Ca2+ Release Channel: Case Study of Dantrolene

2014 ◽  
Vol 21 (8) ◽  
pp. 1062-1072 ◽  
Author(s):  
Karoly Acsai ◽  
Norbert Nagy ◽  
Zoltan Marton ◽  
Kinga Oravecz ◽  
Andras Varro
Keyword(s):  
Ryanodine Receptor ◽  
Release Channel ◽  
Cardiac Ryanodine Receptor
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