Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with substantial morbidity and mortality. It causes profound changes in sarcoplasmic reticulum (SR) Ca(2+) homeostasis, including ryanodine receptor channel dysfunction and diastolic SR Ca(2+) leak, which might contribute to both decreased contractile function and increased propensity to atrial arrhythmias. In this...

Passive SR (sarcoplasmic reticulum) Ca2+ leak through the RyR (ryanodine receptor) plays a critical role in the mechanisms that regulate [Ca2+]rest (intracellular resting myoplasmic free Ca2+ concentration) in muscle. This process appears to be isoform-specific as expression of either RyR1 or RyR3 confers on myotubes different [Ca2+]rest. Using chimaeric RyR3-RyR1 receptors expressed in dyspedi...

Oligomerization of all three mammalian ryanodine receptor isoforms, a structural requirement for normal intracellular Ca2+ release channel function, is displayed by the discrete N-terminal domain which assembles into homo- and hetero-tetramers. This is demonstrated in yeast, mammalian cells and native tissue by complementary yeast two-hybrid, chemical cross-linking and co-immunoprecipitation as...

Although the effects and the underlying mechanism of sympathetic stimulation on cardiac Ca handling are relatively well established both in health and disease, the modes of action and mechanisms of parasympathetic modulation are poorly defined. Here, we demonstrate that parasympathetic stimulation initiates a novel mode of excitation-contraction coupling that enhances the efficiency of cardiac ...

A peptide toxin isolated from the Chinese scorpion Buthus martensi Karsch (BmK-PL) stimulated Ca2+-release channel activity in both triad membranes and reconstituted ryanodine receptors partially purified from rabbit skeletal muscle. In [3H]ryanodine binding experiments, the toxin increased the affinity of ryanodine for the receptor, from a Kd of 24.3 nM to 2.9 nM, which is an enhancement simil...

Mast cells (MCs) are tissue-resident immune cells, which play a pivotal role in skin hypersensitivity reactions. MCs activation via Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) is independent of the classical IgE-mediated pathway, gained much interest recently. Calcium mobilization crucial to mast cell and functional regulation. Ryanodine receptor (RYR) expresses on sarcoplasmic reticulu...

In thelast few decades, the roles of cardio-oncology and cardiovascular geneticsgained more attention in research daily clinical practice, shaping a new approach management patients affected by cancer disease. Genetic characterization undergoing treatment can support better risk stratification beyond typical factors, suchas contractile function QT interval duration, uncovering possible patient’...

Fellner SK, Arendshorst WJ. Voltage-gated Ca entry and ryanodine receptor Ca -induced Ca release in preglomerular arterioles. Am J Physiol Renal Physiol 292: F1568–F1572, 2007. First published December 26, 2006; doi:10.1152/ajprenal.00459.2006.—We have previously shown that in afferent arterioles, angiotensin II (ANG II) involves activation of the inositol trisphosphate receptor (IP3R), activat...

he role of cyclic ADP-ribose in the amplification of subcellular and global Ca 2 signaling upon stimulation of P2Y purinergic receptors was studied in 3T3 fibroblasts. Either (1) 3T3 fibroblasts (CD38 cells), (2) 3T3 fibroblasts preloaded by incubation with extracellular cyclic ADP-ribose (cADPR), (3) 3T3 fibroblasts microinjected with ryanodine, or (4) 3T3 fibroblasts transfected to express th...

Mutations in ryanodine receptor 2 (RYR2) gene can cause catecholaminergic polymorphic ventricular tachycardia (CPVT). The novel RYR2-S4153R mutation has been implicated as a cause of CPVT and atrial fibrillation. The mutation has been functionally characterized via store-overload-induced Ca(2+) release (SOICR) and tritium-labelled ryanodine ([(3)H]ryanodine) binding assays. The S4153R mutation ...