Block by ruthenium red of the ryanodine-activated calcium release channel of skeletal muscle.

Ma, Jianjie

doi:10.1085/jgp.102.6.1031

Cited by 101 publications

(91 citation statements)

References 49 publications

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“…These results suggested that different binding sites are located in the conduction pore of the ryanodine-modified skeletal muscle RyR. Ma (23) did not describe the effects of RR on ryanodine-unmodified RyR1 or RyR2.…”

Section: Discussionmentioning

confidence: 87%

“…Thus, the substates are likely of physiological relevance; however, the dominant mechanism of RR interaction with the Ca 2ϩ -conducting RyRs appears to be full closure. Ma (23) described the effects of RR on the ryanodine-modified skeletal RyR. Several cytosolic RR molecules produced an all-or-none flickery block with a Hill coefficient of 2.…”

Section: Discussionmentioning

confidence: 99%

“…A different effect was observed when ryanodine was used to lock the channels into a permanently open, Ca 2ϩ -insensitive subconductance state. RR blocked single ryanodine-modified skeletal RyRs by binding in a voltage-dependent manner to multiple sites located in the conductance pore of the channel (23).…”

mentioning

confidence: 99%

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Ruthenium Red Modifies the Cardiac and Skeletal Muscle Ca2+ Release Channels (Ryanodine Receptors) by Multiple Mechanisms

Tripathy

Pasek

et al. 1999

Journal of Biological Chemistry

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The effects of ruthenium red (RR) on the skeletal and cardiac muscle ryanodine receptors (RyRs) were studied in vesicle-Ca 2؉ The release and sequestration of Ca 2ϩ ions by the sarcoplasmic reticulum (SR), 1 an intracellular membrane compartment, is essential to the process of cardiac and skeletal muscle contraction and relaxation. The rapid release of Ca 2ϩ is mediated by Ca 2ϩ release channels, also known as ryanodine receptors (RyRs), because they bind the plant alkaloid ryanodine with high affinity and specificity (1-6). Skeletal and cardiac muscles express two major isoforms of the RyR, RyR1 and RyR2, respectively. In striated muscles, RyRs are concentrated in the junctional SR membrane near transverse tubular, voltage-sensitive L-type Ca 2ϩ channels (dihydropyridine receptors). A muscle action potential initiates dihydropyridine receptor conformational changes that activate the RyRs via a direct physical interaction in skeletal muscle or mediate the influx of Ca 2ϩ in cardiac muscle, leading to the release of Ca 2ϩ from the SR and subsequent muscle contraction. Both RyRs have been isolated as 30 S protein complexes composed of four 560-kDa (RyR polypeptide) and four 12-kDa (FK506-binding protein) subunits (1-5). The two channel activities are affected by endogenous and exogenous effectors, such as Ca 2ϩ , Mg 2ϩ , ATP, caffeine, ryanodine, and ruthenium red.Ruthenium red (RR) is one of the most potent inhibitors of SR Ca 2ϩ release (2). RR also inhibits mitochondrial Ca 2ϩ uptake. However, this activity was due to a contaminant (7) that may be related to an oxygen-bridged R360 complex that, at concentrations as high as 10 M, was without effect on SR Ca 2ϩ uptake or release (8). RR is a polycationic dye with a linear structure consisting of three ruthenium atoms with a net valence of 6. In SR vesicles, RR increased the rate of Ca 2ϩ uptake and decreased the rate of Ca 2ϩ release at concentrations ranging from 1 nM to 20 M (9 -18). In muscle fibers, RR concentrations greater than 20 M are required to inhibit SR Ca 2ϩ release because of RR binding to myoplasmic proteins (19,20). In intact single frog twitch muscle fibers, the estimated free RR concentration for half-block of SR Ca 2ϩ release was 2.4 M, in good agreement with the range reported for SR vesicle preparations (19). In [ 3 H]ryanodine binding measurements, RR decreased the B max value and increased the K D value, with the latter effect being due to a slower association rate (16). In single channel measurements, micromolar concentrations of RR decreased the channel open probability of the skeletal (21) and cardiac (22) RyRs by producing prolonged channel closings. A different effect was observed when ryanodine was used to lock the channels into a permanently open, Ca 2ϩ -insensitive subconductance state. RR blocked single ryanodine-modified skeletal RyRs by binding in a voltage-dependent manner to multiple sites located in the conductance pore of the channel (23).The present study was undertaken to clarify the effects of RR on ryanodine-unmodified ...

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Ruthenium Red Modifies the Cardiac and Skeletal Muscle Ca2+ Release Channels (Ryanodine Receptors) by Multiple Mechanisms

Tripathy

Pasek

et al. 1999

Journal of Biological Chemistry

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“…The (18,19), a derivative Ru360 is a more specific and potent inhibitor of mitochondrial Ca 2ϩ uptake (14,15). At the concentrations and pre-incubation times tested, both RuRed and Ru360 have been shown previously (20) to inhibit significantly mitochondrial Ca 2ϩ uptake in intact cells.…”

Section: Cch-and Insp 3 -Evoked Ca 2ϩ Signals Are Significantly Slowementioning

confidence: 99%

Modulation of [Ca2+] Signaling Dynamics and Metabolism by Perinuclear Mitochondria in Mouse Parotid Acinar Cells

Bruce

Giovannucci²,

Blinder

et al. 2004

Journal of Biological Chemistry

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[Ca 2ϩ ] i signals may be tuned to evoke specific physiological responses in these cells. The major function of pancreatic acinar cells is the exocytosis of zymogen granules that can be activated by apically confined [Ca 2ϩ ] i signals (6), suggested to be the major physiological [Ca 2ϩ ] i signal evoked by threshold agonist concentrations (7). These apically confined [Ca 2ϩ ] i signals are in part because of the distribution of mitochondria, which form a belt around the apically located zymogen granules (8, 9). These perigranular mitochondria likely serve two main functions. First, mitochondrial Ca 2ϩ uptake provides a buffer barrier thereby preventing the spread of [Ca 2ϩ ] i waves to the basal part of the cell (8 -10). Second, the Ca 2ϩ taken up by mitochondria drives ATP production locally for the energy-consuming exocytotic process (11). The major function of parotid acinar cells is fluid secretion, and this is most effectively activated by rapid global [Ca 2ϩ ] i signals. We proposed that rapid global [Ca 2ϩ ] i signals facilitate the almost simultaneous activation of Ca 2ϩ -dependent Cl Ϫ channels on the apical membrane and Ca 2ϩ -dependent K ϩ channels on the basolateral membrane (5). The latter maintain the membrane potential at hyperpolarizing potentials and the driving force for Cl Ϫ efflux, thereby ensuring efficient ion and water movement (12). Interestingly, even at threshold stimulation parotid acinar cells exhibit rapid global [Ca 2ϩ ] i signals, and apically confined [Ca 2ϩ ] i signals were never observed (5). Given the many similarities between parotid and pancreatic acinar cells, the differences in the spatial and temporal patterns of [Ca 2ϩ ] i signaling between these two cell types 1 The abbreviations used are: [Ca 2ϩ ] i , intracellular calcium concentration; CCh, carbamylcholine (carbachol); FCCP, carbonyl cyanide 4-trifluoro-methoxyphenylhydrazone; OGB2, Oregon Green BAPTA 2; InsP 3 , inositol 1,4,5-trisphosphate; caged InsP 3 , D-myo-InsP 3 P-4(5)-1-(2-nitrophenyl)-ethyl ester; CaM, calmodulin; RuRed, ruthenium red; NPC, nuclear pore complex; rhod, rhodamine; TRITC, tetramethylrhodamine isothiocyanate.

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“…One type, e.g. ruthenium red [4,5], directly blocks the ryanodine receptor (RyR)/Ca 2÷ channel [6][7][8]. The other type, e.g.…”

Section: Introductionmentioning

confidence: 99%

Neomycin: A novel potent blocker of communication between T‐tubule and sarcoplasmic reticulum

Yano¹,

El-Hayek²,

Antoniu³

et al. 1994

FEBS Letters

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Ca 2÷ release from the sarcoplasmic reticulum (SR) was induced in isolated triads by direct stimulation of the SR moiety by polylysine, or stimulation via chemical depolarization of the transverse tubule (T-tubule) moiety. Polylysine-induced release was blocked by neomycin with an IC50 (the concentration for half-maximal inhibition) of 0.3 pM. However, the IC50 for neomycin block of depolarization-induced Ca 2÷ release sharply decreased in a voltage-dependent fashion, and it was 5.3 nM at a maximal extent of T-tubule depolarization. These results suggest that the high affinity binding of neomycin to the triad leads to the specific blocking of the signal transmission from T-tubule to SR.

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Block by ruthenium red of the ryanodine-activated calcium release channel of skeletal muscle.

Cited by 101 publications

References 49 publications

Ruthenium Red Modifies the Cardiac and Skeletal Muscle Ca2+ Release Channels (Ryanodine Receptors) by Multiple Mechanisms

Ruthenium Red Modifies the Cardiac and Skeletal Muscle Ca2+ Release Channels (Ryanodine Receptors) by Multiple Mechanisms

Modulation of [Ca2+] Signaling Dynamics and Metabolism by Perinuclear Mitochondria in Mouse Parotid Acinar Cells

Neomycin: A novel potent blocker of communication between T‐tubule and sarcoplasmic reticulum

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