H₂O₂activates ryanodine receptor but has little effect on recovery of releasable Ca²⁺content after fatigue

Abstract

We studied whether hydrogen peroxide (H(2)O(2)) at </=10 microM activates the ryanodine receptor and decreases releasable Ca(2+) content in the sarcoplasmic reticulum after fatigue. Exposure of rabbit or frog skeletal muscle ryanodine receptors to 10 microM H(2)O(2) enhanced channel activity in lipid bilayers when the redox potential was defined at cis = -220 mV and trans = -180 mV. Channel activation by 10 microM H(2)O(2) was also observed when cis potential was set at -220 mV without defining trans potential, but the effect was less. Reduction of trans redox potential from -180 to -220 mV did not alter channel activity. H(2)O(2) at 500 microM failed to activate the channel when the redox potential was not controlled. Stimulation of the frog muscle fiber for 2 min (50 Hz, a duty cycle of 200 ms/s) decreased tetanus tension by approximately 50%. After 1 min, tetanus recovered rapidly to approximately 70% of control and thereafter slowly approached the control level. Amplitudes of caffeine- and 4-chloro-m-cresol-induced contractures were decreased after a 60-min rest. The decrease is not enhanced by exposure to 10 microM H(2)O(2). These results suggest that H(2)O(2) markedly activates the ryanodine receptor under the redox control in vitro, but externally applied H(2)O(2) may not play an important role in the postfatigue recovery process.

Hypochlorous acid modifies calcium release channel function from skeletal muscle sarcoplasmic reticulum

“…However, we observed inhibition at 40 M, a concentration much lower than inhibition observed in the binding experiments. This enhanced sensitivity of the channel to various compounds is consistent with observations using H 2 O 2 (14,24) and singlet oxygen (31). It is possible that fusing of a SR vesicle to a bilayer lipid membrane modifies the RyR protein in some manner that enhances its sensitivity to channel activators and inhibitors.…”

“…Both reagents stimulate Ca 2ϩ release from actively loaded vesicles and stimulate the activity of single Ca 2ϩ channel reconstituted into a bilayer lipid membrane. Oba et al (24) demonstrated activation of channel activity in lipid bilayers at 10 M when the channel was under a controlled redox potential. Still, work in more complete or intact systems has not always supported data derived from isolated SR experiments.…”

El acoplamiento excitación-contracción en el músculo esquelético: preguntas por responder a pesar de 50 años de estudio

“…Durante el ejercicio, el músculo y el organismo en general se ven sometidos a un gran estrés oxidativo, es decir, hay una pérdida del equilibrio entre la producción de radicales libres y especies reactivas de oxígeno, Acoplamiento excitación-contracción y la capacidad de las células para manejarlos (121)(122)(123)(124). El aumento de los radicales libres parece alterar la liberación de Ca 2+ desde el retículo sarcoplásmico, aunque el efecto sobre la fatiga muscular no está claro (125)(126)(127), además de disminuir la sensibilidad de la miofibrilla al Ca 2+ en mamíferos (128,129). Se han obtenido resultados contradictorios en cuanto al efecto de los radicales sobre la fuerza máxima de la fibra muscular y sobre el Ca 2+ tetánico (128,.…”

Cross talk between Ca2+and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca2+release channels

“…Skeletal muscle homogenates contain a constitutively active nonphagocytic NAD(P)H oxidase complex that generates superoxide anion (Javesghani et al 2002). Enzymatic or spontaneous dismutation of superoxide anion generates hydrogen peroxide, which markedly activates RyR1 in vitro (Favero et al 1995;Oba et al 2002a) but does not seem to play a significant role in the post fatigue recovery process (Oba et al 2002a). We have found the membrane bound components of NAD(P)H oxidase (gp91 phox and p22 phox ) in skeletal muscle transverse tubules, which are absent from heavy SR vesicles (figure 2).…”

“…Endogenous redox-active molecules, including molecular oxygen (Eu et al 2000) and GSSG (Zable et al 1997;Sun et al 2001a,b;Aracena et al 2003), enhance RyR activity. Likewise, H 2 O 2 markedly activates single RyR2 channels (Boraso & Williams 1994) or RyR1 channels maintained under redox control (provided by controlled cytoplasmic and luminal GSH/GSSG ratios; Oba et al 2002a). Furthermore, superoxide anion generation by a NADH oxidase activity that is present in heavy sarcoplasmic reticulum (SR) vesicles and which copurifies with RyR1 channels is presumably responsible for the activation of [ 3 H]-ryanodine binding (a reflection of increased RyR1 activity) produced by 1 mM NADH (Xia et al 2003).…”