RyR1/SERCA1 cross-talk regulation of calcium transport in heavy sarcoplasmic reticulum vesicles

2003 ◽  
Vol 81 (3) ◽  
pp. 220-233 ◽  
Author(s):  
James S.C Gilchrist ◽  
Chris Palahniuk ◽  
Bernard Abrenica ◽  
Penelope Rampersad ◽  
Mark Mutawe ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Catalytic Activity ◽  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Cross Talk ◽  
Ryanodine Receptors ◽  
Receptor Activation ◽  
Release Channel ◽  
Highly Sensitive

We investigated the functional interdependence of sarco-endoplasmic reticulum Ca2+ ATPase isoform 1 and ryanodine receptor isoform 1 in heavy sarcoplasmic reticulum membranes by synchronous fluorescence determination of extravesicular Ca2+ transients and catalytic activity. Under conditions of dynamic Ca2+ exchange ATPase catalytic activity was well coordinated to ryanodine receptor activation/inactivation states. Ryanodine-induced activation of Ca2+ release channel leaks also produced marked ATPase activation in the absence of measurable increases in bulk free extra vesicular Ca2+. This suggested that Ca2+ pumps are highly sensitive to Ca2+ release channel leak status and potently buffer Ca2+ ions exiting cytoplasmic openings of ryanodine receptors. Conversely, ryanodine receptor activation was dependent on Ca2+-ATPase pump activity. Ryanodine receptor activation by cytosolic Ca2+ was (i) inversely proportional to luminal Ca2+ load and (ii) dependent upon the rate of presentation of cytosolic Ca2+. Progressive Ca2+ filling coincided with progressive loss of Ca2+ sequestration rates and at a threshold loading, ryanodine-induced Ca2+ release produced small transient reversals of catalytic activity. These data indicate that attainment of threshold luminal Ca2+ loads coordinates sensitization of Ca2+ release channels with autogenic inhibition of Ca2+ pumping. This suggests that Ca2+-dependent control of Ca2+ release in intact heavy sarcoplasmic reticulum membranes involves a Ca2+- mediated "cross-talk" between sarco-endoplasmic reticulum Ca2+ ATPase isoform1 and ryanodine receptor isoform 1.Key words: Ca2+, sarcoplasmic reticulum, RyR, SERCA, calsequestrin, ryanodine.

scholarly journals Halothane modulation of skeletal muscle ryanodine receptors: dependence on Ca2+, Mg2+, and ATP

2008 ◽  
Vol 294 (4) ◽  
pp. C1103-C1112 ◽  
Author(s):  
Paula L. Diaz-Sylvester ◽  
Maura Porta ◽  
Julio A. Copello
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Lipid Bilayers ◽  
Ryanodine Receptor ◽  
Genetic Disorder ◽  
Ryanodine Receptors ◽  
Volatile Anesthetic ◽  
Planar Lipid Bilayers ◽  
Wild Type ◽  
Highly Sensitive

Malignant hyperthermia (MH) susceptibility is a genetic disorder of skeletal muscle associated with mutations in the ryanodine receptor isoform 1 (RyR1) of sarcoplasmic reticulum (SR). In MH-susceptible skeletal fibers, RyR1-mediated Ca2+ release is highly sensitive to activation by the volatile anesthetic halothane. Indeed, studies with isolated RyR1 channels (using simple Cs+ solutions) found that halothane selectively affects mutated but not wild-type RyR1 function. However, studies in skeletal fibers indicate that halothane can also activate wild-type RyR1-mediated Ca2+ release. We hypothesized that endogenous RyR1 agonists (ATP, lumenal Ca2+) may increase RyR1 sensitivity to halothane. Consequently, we studied how these agonists affect halothane action on rabbit skeletal RyR1 reconstituted into planar lipid bilayers. We found that cytosolic ATP is required for halothane-induced activation of the skeletal RyR1. Unlike RyR1, cardiac RyR2 (much less sensitive to ATP) responded to halothane even in the absence of this agonist. ATP-dependent halothane activation of RyR1 was enhanced by cytosolic Ca2+ (channel agonist) and counteracted by Mg2+ (channel inhibitor). Dantrolene, a muscle relaxant used to treat MH episodes, did not affect RyR1 or RyR2 basal activity and did not interfere with halothane-induced activation. Studies with skeletal SR microsomes confirmed that halothane-induced RyR1-mediated SR Ca2+ release is enhanced by high ATP-low Mg2+ in the cytosol and by increased SR Ca2+ load. Thus, physiological or pathological processes that induce changes in cellular levels of these modulators could affect RyR1 sensitivity to halothane in skeletal fibers, including the outcome of halothane-induced contracture tests used to diagnose MH susceptibility.

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.

Interaction of Bupivacaine and Tetracaine with the Sarcoplasmic Reticulum Ca2+Release Channel of Skeletal and Cardiac Muscles 

1999 ◽  
Vol 90 (3) ◽  
pp. 835-843 ◽  
Author(s):  
Hirochika Komai ◽  
Andrew J. Lokuta
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Ryanodine Receptor ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Specific Effect ◽  
Receptor Activity ◽  
Maximal Inhibition ◽  
Release Channel

Background Although various local anesthetics can cause histologic damage to skeletal muscle when injected intramuscularly, bupivacaine appears to have an exceptionally high rate of myotoxicity. Research has suggested that an effect of bupivacaine on sarcoplasmic reticulum Ca2+ release is involved in its myotoxicity, but direct evidence is lacking. Furthermore, it is not known whether the toxicity depends on the unique chemical characteristics of bupivacaine and whether the toxicity is found only in skeletal muscle. Methods The authors studied the effects of bupivacaine and the similarly lipid-soluble local anesthetic, tetracaine, on the Ca2+ release channel-ryanodine receptor of sarcoplasmic reticulum in swine skeletal and cardiac muscle. [3H]Ryanodine binding was used to measure the activity of the Ca2+ release channel-ryanodine receptors in microsomes of both muscles. Results Bupivacaine enhanced (by two times at 5 mM) and inhibited (66% inhibition at 10 mM) [3H]ryanodine binding to skeletal muscle microsomes. In contrast, only inhibitory effects were observed with cardiac microsomes (about 3 mM for half-maximal inhibition). Tetracaine, which inhibits [3H]ryanodine binding to skeletal muscle microsomes, also inhibited [3H]ryanodine binding to cardiac muscle microsomes (half-maximal inhibition at 99 microM). Conclusions Bupivacaine's ability to enhance Ca2+ release channel-ryanodine receptor activity of skeletal muscle sarcoplasmic reticulum most likely contributes to the myotoxicity of this local anesthetic. Thus, the pronounced myotoxicity of bupivacaine may be the result of this specific effect on Ca2+ release channel-ryanodine receptor superimposed on a nonspecific action on lipid bilayers to increase the Ca2+ permeability of sarcoplasmic reticulum membranes, an effect shared by all local anesthetics. The specific action of tetracaine to inhibit Ca2+ release channel-ryanodine receptor activity may in part counterbalance the nonspecific action, resulting in moderate myotoxicity.

cADP-ribose releases Ca2+ from cardiac sarcoplasmic reticulum independently of ryanodine receptor

1997 ◽  
Vol 273 (3) ◽  
pp. H1082-H1089 ◽  
Author(s):  
P. Lahouratate ◽  
J. Guibert ◽  
J. F. Faivre
Keyword(s):  
Endoplasmic Reticulum ◽  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Sea Urchin ◽  
Calcium Release ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Consistent Effect ◽  
Cyclic Adp Ribose

Cyclic ADP-ribose (cADPR), an endogenous metabolite of beta-NAD+, activates Ca2+ release from endoplasmic reticulum in sea urchin eggs via the ryanodine receptor (RyR) pathway. A similar role has been proposed in cardiac sarcoplasmic reticulum (SR), although this remains controversial. We therefore investigated the ability of cADPR to induce Ca2+ release from canine cardiac SR microsomes using fluo 3 to monitor extravesicular Ca2+ concentration. We found that cADPR induced Ca2+ release in a concentration-dependent manner, whereas neither its precursor, NAD+, nor its metabolite, ADP-ribose, elicited a consistent effect. In addition, an additive effect on calcium release between cADPR and 9-Me-7-Br-eudistomin-D (MBED), an activator of RyR, was found as well as no cross-desensitization between cADPR and MBED. Specific blockers of the RyR did not abolish the cADPR-induced Ca2+ release. These results provide evidence for cADPR-induced Ca2+ release from dog cardiac SR via a novel mechanism which is independent of RyR activation.

scholarly journals Aldolase potentiates DIDS activation of the ryanodine receptor in rabbit skeletal sarcoplasmic reticulum

2006 ◽  
Vol 399 (2) ◽  
pp. 325-333 ◽  
Author(s):  
In-Ra Seo ◽  
Sang Hyun Moh ◽  
Eun Hui Lee ◽  
Gerhard Meissner ◽  
Do Han Kim
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Column Chromatography ◽  
Anion Channel ◽  
Affinity Column ◽  
Open Probability ◽  
Release Channel ◽  
Affinity Column Chromatography ◽  
Lifetime Analysis ◽  
Associated Proteins

DIDS (4,4′-di-isothiocyanostilbene-2,2′-disulfonate), an anion channel blocker, triggers Ca2+ release from skeletal muscle SR (sarcoplasmic reticulum). The present study characterized the effects of DIDS on rabbit skeletal single Ca2+-release channel/RyR1 (ryanodine receptor type 1) incorporated into a planar lipid bilayer. When junctional SR vesicles were used for channel incorporation (native RyR1), DIDS increased the mean Po (open probability) of RyR1 without affecting unitary conductance when Cs+ was used as the charge carrier. Lifetime analysis of single RyR1 activities showed that 10 μM DIDS induced reversible long-lived open events (Po=0.451±0.038) in the presence of 10 μM Ca2+, due mainly to a new third component for both open and closed time constants. However, when purified RyR1 was examined in the same condition, 10 μM DIDS became considerably less potent (Po=0.206±0.025), although the caffeine response was similar between native and purified RyR1. Hence we postulated that a DIDS-binding protein, essential for the DIDS sensitivity of RyR1, was lost during RyR1 purification. DIDS-affinity column chromatography of solubilized junctional SR, and MALDI–TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS analysis of the affinity-column-associated proteins, identified four major DIDS-binding proteins in the SR fraction. Among them, aldolase was the only protein that greatly potentiated DIDS sensitivity. The association between RyR1 and aldolase was further confirmed by co-immunoprecipitation and aldolase-affinity batch-column chromatography. Taken together, we conclude that aldolase is physically associated with RyR1 and could confer a considerable potentiation of the DIDS effect on RyR1.

scholarly journals Thimerosal Interacts with the Ca2+ Release Channel Ryanodine Receptor from Skeletal Muscle Sarcoplasmic Reticulum

1995 ◽  
Vol 270 (50) ◽  
pp. 29644-29647 ◽  
Author(s):  
Jonathan J. Abramson ◽  
Anthony C. Zable ◽  
Terence G. Favero ◽  
Guy Salama
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Release Channel
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