FKBPs facilitate the termination of spontaneous Ca2+ release in wild-type RyR2 but not CPVT mutant RyR2

2016 ◽  
Vol 473 (14) ◽  
pp. 2049-2060 ◽  
Author(s):  
Joe Z. Zhang ◽  
Helen M.M. Waddell ◽  
Ella Wu ◽  
Jhanvi Dholakia ◽  
Chidinma A. Okolo ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Binding Proteins ◽  
Wild Type ◽  
Fk506 Binding Proteins ◽  
Cardiac Ryanodine Receptor

We show that the magnitude of Ca2+ release through the cardiac ryanodine receptor (RyR2) is controlled by the presence of FK506-binding proteins but that this regulation is lost when arrhythmogenic RyR2 mutations are present.

scholarly journals Mineralocorticoid Modulation of Cardiac Ryanodine Receptor Activity Is Associated With Downregulation of FK506-Binding Proteins

Circulation ◽  
2009 ◽  
Vol 119 (16) ◽  
pp. 2179-2187 ◽  
Author(s):  
Ana María Gómez ◽  
Angélica Rueda ◽  
Yannis Sainte-Marie ◽  
Laetitia Pereira ◽  
Spyros Zissimopoulos ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Binding Proteins ◽  
Receptor Activity ◽  
Fk506 Binding Proteins ◽  
Cardiac Ryanodine Receptor

scholarly journals N-terminal and Central Segments of the Type 1 Ryanodine Receptor Mediate Its Interaction with FK506-binding Proteins

2013 ◽  
Vol 288 (22) ◽  
pp. 16073-16084 ◽  
Author(s):  
Tanya Girgenrath ◽  
Mohana Mahalingam ◽  
Bengt Svensson ◽  
Florentin R. Nitu ◽  
Razvan L. Cornea ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Binding Proteins ◽  
Fk506 Binding Proteins

scholarly journals Flecainide Paradoxically Activates Cardiac Ryanodine Receptor Channels under Low Activity Conditions: A Potential Pro-Arrhythmic Action

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2101
Author(s):  
Samantha C. Salvage ◽  
Esther M. Gallant ◽  
James A. Fraser ◽  
Christopher L.-H. Huang ◽  
Angela F. Dulhunty
Keyword(s):  
Atrial Fibrillation ◽  
Ryanodine Receptor ◽  
Polymorphic Ventricular Tachycardia ◽  
Sodium Currents ◽  
Wild Type ◽  
Open Probability ◽  
Active Channels ◽  
Separate Activation ◽  
Low Activity ◽  
Cardiac Ryanodine Receptor

Cardiac ryanodine receptor (RyR2) mutations are implicated in the potentially fatal catecholaminergic polymorphic ventricular tachycardia (CPVT) and in atrial fibrillation. CPVT has been successfully treated with flecainide monotherapy, with occasional notable exceptions. Reported actions of flecainide on cardiac sodium currents from mice carrying the pro-arrhythmic homozygotic RyR2-P2328S mutation prompted our explorations of the effects of flecainide on their RyR2 channels. Lipid bilayer electrophysiology techniques demonstrated a novel, paradoxical increase in RyR2 activity. Preceding flecainide exposure, channels were mildly activated by 1 mM luminal Ca2+ and 1 µM cytoplasmic Ca2+, with open probabilities (Po) of 0.03 ± 0.01 (wild type, WT) or 0.096 ± 0.024 (P2328S). Open probability (Po) increased within 0.5 to 3 min of exposure to 0.5 to 5.0 µM cytoplasmic flecainide, then declined with higher concentrations of flecainide. There were no such increases in a subset of high Po channels with Po ≥ 0.08, although Po then declined with ≥5 µM (WT) or ≥50 µM flecainide (P2328S). On average, channels with Po < 0.08 were significantly activated by 0.5 to 10 µM of flecainide (WT) or 0.5 to 50 µM of flecainide (P2328S). These results suggest that flecainide can bind to separate activation and inhibition sites on RyR2, with activation dominating in lower activity channels and inhibition dominating in more active channels.

scholarly journals Disparities in the association of the ryanodine receptor and the FK506-binding proteins in mammalian heart

2012 ◽  
Vol 125 (7) ◽  
pp. 1759-1769 ◽  
Author(s):  
S. Zissimopoulos ◽  
S. Seifan ◽  
C. Maxwell ◽  
A. J. Williams ◽  
F. A. Lai
Keyword(s):  
Ryanodine Receptor ◽  
Binding Proteins ◽  
Mammalian Heart ◽  
Fk506 Binding Proteins

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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