Search results for "Ryanodine receptor"

More than a pore: How voltage-gated calcium channels act on different levels of neuronal communication regulation.

2021

ABSTRACT Voltage-gated calcium channels (VGCCs) represent key regulators of the calcium influx through the plasma membrane of excitable cells, like neurons. Activated by the depolarization of the membrane, the opening of VGCCs induces very transient and local changes in the intracellular calcium concentration, known as calcium nanodomains, that in turn trigger calcium-dependent signaling cascades and the release of chemical neurotransmitters. Based on their central importance as concierges of excitation-secretion coupling and therefore neuronal communication, VGCCs have been studied in multiple aspects of neuronal function and malfunction. However, studies on molecular interaction partners …

Nickel induces intracellular calcium mobilization and pathophysiological responses in human cultured airway epithelial cells.

2009

Abstract Environmental exposure to nickel is associated to respiratory disorders and potential toxicity in the lung but molecular mechanisms remain incompletely explored. The extracellular Ca 2+ -sensing receptor (CaSR) is widely distributed and may be activated by divalent cations. In this study, we investigated the presence of CaSR in human cultured airway epithelial cells and its activation by nickel. Nickel transiently increased intracellular calcium (−log EC 50  = 4.67 ± 0.06) in A549 and human bronchial epithelial cells as measured by epifluorescence microscopy. Nickel (20 μM)-induced calcium responses were reduced after thapsigargin or ryanodine exposure but not by Ca 2+ -free medium…

Signal transduction pathways involved in the mechanical responses to protease-activated receptors in rat colon.

2002

Recording simultaneously in vitro the changes of endoluminal pressure (index of circular muscle activity) and isometric tension (index of longitudinal muscle activity), we examined the mechanisms responsible for the apamin-sensitive relaxant and contractile responses induced by protease-activated receptor (PAR)-1 and PAR-2 activating peptides, SFLLRN-NH2 and SLIGRL-NH2, respectively, in rat colon. In the circular muscle, the inhibitory effects of SFLLRN-NH2 and SLIGRL-NH2 were significantly reduced by ryanodine, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, but unaffected by 1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122), a phosph…

The spasmogenic effects of vanadate in human isolated bronchus

1997

1. Inhalation of vanadium compounds, particularly vanadate, is a cause of occupational bronchial asthma. We have now studied the action of vanadate on human isolated bronchus. Vanadate (0.1 microM-3 mM) produced concentration-dependent, well-sustained contraction. Its -logEC50 was 3.74 +/- 0.05 (mean +/- s.e.mean) and its maximal effect was equivalent to 97.5 +/- 4.2% of the response to acetylcholine (ACh, 1 mM). 2. Vanadate (200 microM)-induced contraction of human bronchus was epithelium-independent and was not inhibited by indomethacin (2.8 microM), zileuton (10 microM), a mixture of atropine, mepyramine and phentolamine (each at 1 microM), or by mast cell degranulation with compound 48/…

Mechanism of Sinoatrial Node Dysfunction in a RyR 2 R420Q Mouse Model Ofcatecholaminergic Polymorphic Ventricular Tachycardia

2017

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disease characterized by stress-induced syncope and/or sudden death in young individuals with structurally normal heart. More than 150 mutations located in the cardiac Ca2+ release channel (type-2 ryanodine receptor, RyR2) gene are related to CPVT. Besides ventricular tachycardia (VT) under stress, sinoatrial node (SAN) dysfunction is frequently observed in CPVT patients. However, the cellular mechanisms remain underexplored. We created a KI mice model bearing a mutation in the N-terminal portion of the RyR2 found in a CPVT family, RyR2(R420Q). ECGs were recorded in KI and WT littermates in resting condition and after…

Characterization of a Ryanodine Receptor inPeriplaneta Americana

1997

Specific binding sites for the alkaloid ryanodine were characterized in membrane preparations from sarcoplasmatic reticulum of Periplaneta americana skeletal muscle. Binding of [3H]ryanodine was optimal at pH 8 and at CaCl2 concentration of about 300 mumol l-1. The Ca-chelating agents EGTA (100 mumol l-1) and EDTA (100 mumol l-1) abolished 95% and 90% of the [3H]ryanodine binding respectively. Preincubation with Ca2+ (100 mumol l-1) restored the ryanodine binding in presence of up to 300 mumol l-1 EGTA. Radioligand binding experiments showed one class of high affinity binding sites for ryanodine. Determination of rate constants revealed 7.05 x 10(6) l mol-1 min-1 for associating and 3.77 x …

Understanding symptoms in RYR1-Related Myopathies: A mixed-methods analysis based on participants' experience

2020

Background: In rare diseases such as ryanodine receptor 1-related myopathies (RYR1-RM), health-related quality of life (HRQoL) measures are critically important so clinicians and researchers can better understand what symptoms are most important to participants, with the ultimate goal of finding tangible solutions for them. Objectives: The main objective of this study was to characterize symptoms in individuals with RYR1-RM to inform future research. A secondary objective of this study was to analyze positive and negative sentiments regarding symptoms and treatment effects post N-acetylcysteine (NAC) administration in individuals with RYR1-RM. Methods: The study used a mixed-methods design …

Mechanisms of Ca2+ liberation at fertilization

2005

The mechanisms underlying the Ca2+ release at fertilization of several animal organisms are reported. Four main classical theories are described, i.e., that of Ca2+ release following simple sperm contact and a G protein stimulation; that of simple sperm contact followed by a tyrosine kinase receptor activation; that of the necessity of introduction by sperm into the egg of molecules for Ca2+ release; and that the molecule introduced into the marine eggs for Ca2+ release is the same Ca2+. Two other mechanisms for Ca2+ release are also illustrated: that of ryanodine receptor stimulation and that of NAADP formation.

2017

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic arrhythmia that manifests syncope or sudden death in children and young adults under stress conditions. CPVT patients often present bradycardia and sino-atrial node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN function in two CPVT families and in a novel knock-in (KI) mouse model carrying the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate. Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was slower in KI mouse SAN preparations than in WT, without any significant alteration in the "funny" current (If ). The L-type Ca2+ current …

A 35-year effective treatment of catecholaminergic polymorphic ventricular tachycardia with propafenone

2018

Key Teaching Points • Despite proven catecholaminergic polymorphic ventricular tachycardia (CPVT) with pathogen RyR2 mutation and recurrent syncope, patients could have a favorable long-term outcome over 35 years under treatment. • Propafenone could be effective for treatment of patients with CPVT. • The beneficial effect of the monotherapy with propafenone in our patient may result from the combined antiarrhythmic effect of this drug with Na+ channel blockade and beta blocker capabilities.