Calcium Release Channels (Ryanodine Receptors) and Arrhythmogenesis

2008 ◽  
pp. 218-231
Author(s):  
Subeena Sood ◽  
Xander H.T. Wehrens
Keyword(s):  
Calcium Release ◽  
Ryanodine Receptors ◽  
Calcium Release Channels

scholarly journals Phosphorylation-Dependent Regulation of Ryanodine Receptors

2001 ◽  
Vol 153 (4) ◽  
pp. 699-708 ◽  
Author(s):  
Steven O. Marx ◽  
Steven Reiken ◽  
Yuji Hisamatsu ◽  
Marta Gaburjakova ◽  
Jana Gaburjakova ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Rapid Identification ◽  
Calcium Release Channels ◽  
Macromolecular Complexes ◽  
Protein Binding Sites ◽  
Skeletal Muscle Contraction

Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function.

Sarcoplasmic Reticulum Calcium Release Channels in Ventricles of Older Adult Hamsters

2006 ◽  
Vol 25 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Peter A. Nicholl ◽  
Susan E. Howlett
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Older Adult ◽  
Binding Sites ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Calcium Release Channels ◽  
Site Density ◽  
Age Related ◽  
Sarcoplasmic Reticulum Calcium ◽  
Age Related Changes

ABSTRACTWhether the density of sarcoplasmic reticulum (SR) calcium release channels / ryanodine receptors in the heart declines with age is not clear. We investigated age-related changes in the density of «3H»-ryanodine receptors in crude ventricular homogenates, which contained all ligand binding sites in heart and in isolated junctional SR membranes. Experiments utilized young (120 days) and older adult (300 days) hamsters. «3H»-ryanodine binding site density did not change with age in crude homogenate preparations, although total heart protein concentration increased significantly with age. In contrast, the density of «3H»-ryanodine binding sites decreased markedly in heavy SR membranes purified from older hearts. These results show that demonstration of age-related changes in cardiac ryanodine receptor density depends upon the preparation used. Furthermore, the increase in total ventricular protein with age suggests that normalization of data by membrane protein should be used with caution in studies of aging heart.

scholarly journals Calcium signaling via two-pore channels: local or global, that is the question

2010 ◽  
Vol 298 (3) ◽  
pp. C430-C441 ◽  
Author(s):  
Michael X. Zhu ◽  
Jianjie Ma ◽  
John Parrington ◽  
Peter J. Calcraft ◽  
Antony Galione ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Calcium Stores ◽  
Calcium Signals ◽  
Calcium Release Channels ◽  
Intracellular Calcium Signaling ◽  
Global Signal ◽  
Rna Knockdown ◽  
Calcium Induced Calcium Release

Recently, we identified, for the first time, two-pore channels (TPCs, TPCN for gene name) as a novel family of nicotinic acid adenine dinucleotide phosphate (NAADP)-gated, endolysosome-targeted calcium release channels. Significantly, three subtypes of TPCs have been characterized, TPC1-3, with each being targeted to discrete acidic calcium stores, namely lysosomes (TPC2) and endosomes (TPC1 and TPC3). That TPCs act as NAADP-gated calcium release channels is clear, given that NAADP binds to high- and low-affinity sites associated with TPC2 and thereby induces calcium release and homologous desensitization, as observed in the case of endogenous NAADP receptors. Moreover, NAADP-evoked calcium signals via TPC2 are ablated by short hairpin RNA knockdown of TPC2 and by depletion of acidic calcium stores with bafilomycin. Importantly, however, NAADP-evoked calcium signals were biphasic in nature, with an initial phase of calcium release from lysosomes via TPC2, being subsequently amplified by calcium-induced calcium release (CICR) from the endoplasmic reticulum (ER). In marked contrast, calcium release via endosome-targeted TPC1 induced only spatially restricted calcium signals that were not amplified by CICR from the ER. These findings provide new insights into the mechanisms that cells may utilize to “filter” calcium signals via junctional complexes to determine whether a given signal remains local or is converted into a propagating global signal. Essentially, endosomes and lysosomes represent vesicular calcium stores, quite unlike the ER network, and TPCs do not themselves support CICR or, therefore, propagating regenerative calcium waves. Thus “quantal” vesicular calcium release via TPCs must subsequently recruit inositol 1,4,5-trisphoshpate receptors and/or ryanodine receptors on the ER by CICR to evoke a propagating calcium wave. This may call for a revision of current views on the mechanisms of intracellular calcium signaling. The purpose of this review is, therefore, to provide an appropriate framework for future studies in this area.

scholarly journals Coordinated Incorporation of Skeletal Muscle Dihydropyridine Receptors and Ryanodine Receptors in Peripheral Couplings of BC3H1 Cells

1997 ◽  
Vol 137 (4) ◽  
pp. 859-870 ◽  
Author(s):  
Feliciano Protasi ◽  
Clara Franzini-Armstrong ◽  
Bernhard E. Flucher
Keyword(s):  
Skeletal Muscle ◽  
Calcium Release ◽  
Surface Membrane ◽  
Ryanodine Receptors ◽  
Freeze Fracture ◽  
Cell Periphery ◽  
Calcium Release Channels ◽  
Transverse Tubular System ◽  
Dihydropyridine Receptors ◽  
Tubular System

Rapid release of calcium from the sarcoplasmic reticulum (SR) of skeletal muscle fibers during excitation–contraction (e–c) coupling is initiated by the interaction of surface membrane calcium channels (dihydropyridine receptors; DHPRs) with the calcium release channels of the SR (ryanodine receptors; RyRs, or feet). We studied the early differentiation of calcium release units, which mediate this interaction, in BC3H1 cells. Immunofluorescence labelings of differentiating myocytes with antibodies against α1 and α2 subunits of DHPRs, RyRs, and triadin show that the skeletal isoforms of all four proteins are abundantly expressed upon differentiation, they appear concomitantly, and they are colocalized. The transverse tubular system is poorly organized, and thus clusters of e–c coupling proteins are predominantly located at the cell periphery. Freeze fracture analysis of the surface membrane reveals tetrads of large intramembrane particles, arranged in orderly arrays. These appear concomitantly with arrays of feet (RyRs) and with the appearance of DHPR/RyS clusters, confirming that the four components of the tetrads correspond to skeletal muscle DHPRs. The arrangement of tetrads and feet in developing junctions indicates that incorporation of DHPRs in junctional domains of the surface membrane proceeds gradually and is highly coordinated with the formation of RyR arrays. Within the arrays, tetrads are positioned at a spacing of twice the distance between the feet. The incorporation of individual DHPRs into tetrads occurs exclusively at positions corresponding to alternate feet, suggesting that the assembly of RyR arrays not only guides the assembly of tetrads but also determines their characteristic spacing in the junction.

scholarly journals The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues.

1995 ◽  
Vol 128 (5) ◽  
pp. 893-904 ◽  
Author(s):  
G Giannini ◽  
A Conti ◽  
S Mammarella ◽  
M Scrobogna ◽  
V Sorrentino
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Intracellular Calcium ◽  
Ryanodine Receptor ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Calcium Release Channels ◽  
Peripheral Tissues ◽  
The Central Nervous System

Ryanodine receptors (RyRs) are intracellular calcium release channels that participate in controlling cytosolic calcium levels. At variance with the probably ubiquitous inositol 1,4,5-trisphosphate-operated calcium channels (1,4,5-trisphosphate receptors), RyRs have been mainly regarded as the calcium release channels controlling skeletal and cardiac muscle contraction. Increasing evidence has recently suggested that RyRs may be more widely expressed, but this has never been extensively examined. Therefore, we cloned three cDNAs corresponding to murine RyR homologues to carry a comprehensive analysis of their expression in murine tissues. Here, we report that the three genes are expressed in almost all tissues analyzed, where tissue-specific patterns of expression were observed. In the uterus and vas deferens, expression of RyR3 was localized to the smooth muscle component of these organs. In the testis, expression of RyR1 and RyR3 was detected in germ cells. RyR mRNAs were also detected in in vitro-cultured cell lines. RyR1, RyR2, and RyR3 mRNA were detected in the cerebrum and in the cerebellum. In situ analysis revealed a cell type-specific pattern of expression in the different regions of the central nervous system. The differential expression of the three ryanodine receptor genes in the central nervous system was also confirmed using specific antibodies against the respective proteins. This widespread pattern of expression suggests that RyRs may participate in the regulation of intracellular calcium homeostasis in a range of cells wider than previously recognized.

scholarly journals SH Oxidation Stimulates Calcium Release Channels (Ryanodine Receptors) From Excitable Cells

2000 ◽  
Vol 33 (2) ◽  
Author(s):  
CECILIA HIDALGO ◽  
RICARDO BULL ◽  
JUAN J MARENGO ◽  
CLAUDIO F PÉREZ ◽  
PAULINA DONOSO
Keyword(s):  
Calcium Release ◽  
Ryanodine Receptors ◽  
Excitable Cells ◽  
Calcium Release Channels

The geometry of the EJSR Z-rete in avian cardiac muscle

1995 ◽  
Vol 53 ◽  
pp. 940-941
Author(s):  
J.R. Sommer ◽  
T. High ◽  
I. Taylor
Keyword(s):  
Cardiac Muscle ◽  
Muscle Activation ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Alternative Mechanism ◽  
Calcium Release Channels ◽  
Graded Response ◽  
Calcium Induced Calcium Release ◽  
Theoretical Considerations ◽  
Recent Demonstration

The junctional SRs (JSR) in skeletal and cardiac muscle in general, including extended junctional SR (EJSR) in avian hearts, are morphologic and functional homologies as shown by biochemical and morphometric evidence, including the recent demonstration that EJSR contains ryanodine receptors and binds [3H]-Ryanodine. Bird hearts have two aberrant membrane features: 1. absence of transverse tu-bules (TT) and, 2. extension of JSRs (thus: E-JSR) from peripheral couplings into the interior of the myocytes forming EJSR Z-retes that both surround and pervade Z-discs. Absence of TT calls for an alternative mechanism for global muscle activation in bird hearts for which EJSR may provide the anatomical substratum, a possibility supported by both experimental evidence, and recent theoretical considerations. Propagated calcium-induced calcium release (CICR) has been difficult to reconcile with the graded response of cardiac muscle to stimulation.2,cf.5 Propagation of an action potential along the Z-retes can be excluded. In the absence of TT, saltatory CICR as an alternative to propagated cardiac activation, is made plausible by the existence of EJSR which, (a) is demonstrably calcium-sensitive, (b) is well within < than 0.5μm of the regulatory proteins of cardiac myocytes and, (c) carries rows of proven, vicinal calcium release channels.

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