Inhibition of the skeletal muscle ryanodine receptor calcium release channel by nitric oxide

Mészáros, LászlóG.; Minarovic, Igor; Zahradníková, Alexandra

doi:10.1016/0014-5793(96)00003-8

Cited by 133 publications

(81 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to oxidants, NO decreases contractile force generation in unfatigued skeletal muscle (4). Mèszá ros et al (8,9) reported an inhibitory effect of NO on RYR1 activity which would explain the decrease in contractile function. In our experiments, NO donors at lower concentrations did not change channel activity but did inhibit intersubunit cross-linking and prevent the activation of RYR1 by oxidants.…”

Section: Discussionmentioning

confidence: 98%

“…The exact nature of the effects of NO compounds on RYR1 is, however, controversial. Mèszá ros et al (8,9) observed inhibition of the RYR1 channel activity by NO donors, whereas Stoyanovsky et al (10,11) found that NO donors activate RYR1. Both groups postulated that these effects are mediated by the reaction of NO with sulfhydryls on the Ca 2ϩ release channel.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Nitric Oxide Protects the Skeletal Muscle Ca2+Release Channel from Oxidation Induced Activation

Aghdasi¹,

Reid²,

Hamilton³

1997

Journal of Biological Chemistry

125

105

View full text Add to dashboard Cite

Reactive oxygen intermediates and nitric oxide modulate the contractile function of skeletal muscle fibers, possibly via direct interaction with the Ca 2؉ release channel. Oxidants produce disulfide bonds between subunits of the Ca 2؉ release channel tetramer, and this is accompanied by an increase in channel activity. The sulfhydryl alkylating agent N-ethylmaleimide has three distinct effects on Ca 2؉ release channel activity: first, channel activity is decreased (phase 1); then with continued exposure the activity is dramatically increased (phase 2); and finally, the channel is again inhibited Nitric oxide (NO 1 ; including NO ϩ , NO Ϫ , and NO ⅐ (2)) and reactive oxygen intermediates (ROI) are produced in skeletal muscle and modulate excitation-contraction coupling (3, 4). One model to explain these effects is that endogenous NO and ROI influence calcium homeostasis (5) by directly altering the activity of the skeletal muscle Ca 2ϩ release channel (RYR1). Favero et al. (6) reported a biphasic effect of H 2 O 2 on skeletal muscle RYR1; first it activated and then it inhibited the channel. Activation of the channel with H 2 O 2 was reversible with reducing agents such as dithiothreitol (DTT). These workers proposed that the increase in channel activity is due to the formation of cross-links between the RYR1 and triadin (6, 7). We (1) demonstrated that diamide produces disulfide bonds between subunits of the RYR1 tetramer and proposed that this cross-linking activates the channel. In these studies we also demonstrated that alkylation of RYR1 by N-ethylmaleimide (NEM) has triphasic effects on single channel activity and on [ 3 H]ryanodine binding. Alkylation of hyperactive (phase 1) sulfhydryls and oxidative cross-linking of sulfhydryls are mutually exclusive processes; either can occur but not both.NO generating compounds have also been shown to alter the activity of RYR1. The exact nature of the effects of NO compounds on RYR1 is, however, controversial. Mèszá ros et al. (8,9) observed inhibition of the RYR1 channel activity by NO donors, whereas Stoyanovsky et al. (10,11) found that NO donors activate RYR1. Both groups postulated that these effects are mediated by the reaction of NO with sulfhydryls on the Ca 2ϩ release channel. The divergent effects of NO on Ca 2ϩ release channel could arise from differences in 1) the reaction conditions, 2) the amount of NO generated, or 3) the reaction by-products. ROI enhance contractile function, whereas NO opposes this effect (3-5). In this study we test the hypothesis that oxidants and NO interact directly with RYR1; oxidants activate the channel, and NO blocks the oxidative activation. Diamide cross-linking and NEM alkylation are used as tools to elucidate the mechanism of interaction of oxidants and NO with the functional sulfhydryls of RYR1.

show abstract

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Nitric Oxide Protects the Skeletal Muscle Ca2+Release Channel from Oxidation Induced Activation

Aghdasi¹,

Reid²,

Hamilton³

1997

Journal of Biological Chemistry

125

105

View full text Add to dashboard Cite

show abstract

“…A possible explanation for this threshold might be a NO-dependent reduction in skeletal muscle force via modulation of excitation-contraction coupling. It has been reported that the opening of the Ca 2ϩ release channels of the sarcoplasmic reticulum (SR) is inhibited by NO (32,35) and highly related to NO availability (35). In addition, Ca 2ϩ transport (35), SR Ca 2ϩ -ATPase activity (18), and cytochrome c-oxidase inhibition (9) may be influenced by NO and contribute to a dose-dependent modulation of excitation-contraction coupling.…”

Section: Dose Response: Severe-intensity Exercisementioning

confidence: 99%

Beetroot juice and exercise: pharmacodynamic and dose-response relationships

Wylie

Kelly

Bailey

et al. 2013

Journal of Applied Physiology

420

449

View full text Add to dashboard Cite

Ϫ ] increased in a dose-dependent manner, with the peak changes occurring at approximately 2-3 h. Compared with PL, 70 ml BR did not alter the physiological responses to exercise. However, 140 and 280 ml BR reduced the steady-state oxygen (O2) uptake during moderateintensity exercise by 1.7% (P ϭ 0.06) and 3.0% (P Ͻ 0.05), whereas time-to-task failure was extended by 14% and 12% (both P Ͻ 0.05), respectively, compared with PL. The results indicate that whereas plasma [NO 2 Ϫ ] and the O2 cost of moderate-intensity exercise are altered dose dependently with NO 3 Ϫ -rich BR, there is no additional improvement in exercise tolerance after ingesting BR containing 16.8 compared with 8.4 mmol NO 3 Ϫ . These findings have important implications for the use of BR to enhance cardiovascular health and exercise performance in young adults.nitrate; nitrite; nitric oxide; blood pressure; exercise economy; O2 uptake; exercise tolerance NITRIC OXIDE (NO) IS A GASEOUS signaling molecule that modulates human physiological function via its role in, for example, the regulation of blood flow, neurotransmission, immune function, glucose and calcium homeostasis, muscle contractility, and mitochondrial respiration (9, 36). 1 NO is generated through the oxidation of the amino acid L-arginine Ϫ ] peaked 3 h postingestion, remained close to peak values until 5 h postingestion, and returned to baseline after 24 h (39). The systolic and diastolic BP and the mean arterial pressure (MAP) were reduced significantly, by ϳ10, ϳ8, and ϳ8 mmHg, respectively, at 2.5-3 h after BR intake. The same research group later reported a dose-dependent increase in plasma [ ] was accompanied by significant reductions in both systolic BP (of ϳ2, ϳ6, and ϳ9 mmHg, respectively) and diastolic BP (of ϳ4, ϳ4, and ϳ6 mmHg, respectively). However, since BR contains polyphenols and antioxidants, which can facilitate the synthesis of NO from NO 2 Ϫ in the stomach (30), it is unclear whether BP is similarly impacted when different doses of BR are ingested compared with equivalent doses of NO 3 Ϫ salts. Given the growing interest in dietary NO 3 Ϫ supplementation in the form of BR amongst athletes and the general population, it is important to determine the pharmacokinetic-pharmacodynamic relationship between different volumes of BR consumption and changes in plasma [NO 2 Ϫ ] and BP to establish an optimal dose for beneficial effects.Recent investigations suggest that dietary NO 3 Ϫ supplementation has the potential to influence human physiology beyond 1 This article is the topic of an Invited Editorial by L. Burke (5a).

show abstract

“…Accordingly, it has been suggested that more durable and potent SNOs of glutathione or cysteine may contribute to EDRF activity. 8 SNOs have both potent vasorelaxant 9 and platelet inhibitory properties 10,11 involving activation of soluble guanylate cyclase as well as cGMPindependent actions, including direct modulation of membrane-associated ion channels 12 and enzymes. 13 This broad range of activity reflects the ability of SNOs to regulate both heme-and thiol-containing proteins.…”

mentioning

confidence: 99%

Cell-Free and Erythrocytic S -Nitrosohemoglobin Inhibits Human Platelet Aggregation

1998

View full text Add to dashboard Cite

Background-Nitric oxide (NO) and related molecules are thought to inhibit human platelet aggregation by raising levels of cGMP. Methods and Results-Both oxidative stress (reactive oxygen species) and hemoglobin (Hb) seem to oppose NO effects. A major fraction of NO in the blood is bound to thiols of Hb, forming S-nitrosohemoglobin (SNO-Hb), which releases the NO group on deoxygenation in the microcirculation. Here we show that (1) both cell-free and intraerythrocytic SNO-Hb (SNO-RBC) inhibit platelet aggregation, (2) the oxidation state of the hemes in Hb influences the response-SNOmetHb (which is functionally similar to SNO-deoxyHb) has greater platelet inhibitory effects than SNO-oxyHb, and (3) the mechanism of platelet inhibition by SNO-Hb is cGMP independent. Conclusions-We suggest that the RBC has evolved a means to counteract platelet activation in small vessels and the proaggregatory effects of oxidative stress by forming SNO-Hb. (Circulation. 1998;97:263-267.)

show abstract

Inhibition of the skeletal muscle ryanodine receptor calcium release channel by nitric oxide

Cited by 133 publications

References 22 publications

Nitric Oxide Protects the Skeletal Muscle Ca2+Release Channel from Oxidation Induced Activation

Nitric Oxide Protects the Skeletal Muscle Ca2+Release Channel from Oxidation Induced Activation

Beetroot juice and exercise: pharmacodynamic and dose-response relationships

Cell-Free and Erythrocytic S -Nitrosohemoglobin Inhibits Human Platelet Aggregation

Contact Info

Product

Resources

About