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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of quercetin on single Ca(2+) release channel behavior of skeletal muscle.

Quercetin, a bioflavonoid, is known to affect Ca(2+) fluxes in sarcoplasmic reticulum, although its direct effect on Ca(2+) release channel (CRC) in sarcoplasmic reticulum has remained to be elucidated. The present study examined the effect of quercetin on the behavior of single skeletal CRC in planar lipid bilayer. The effect of caffeine was also studied for comparison. At very low [Ca(2+)](cis) (80 pM), quercetin activated CRC marginally, whereas at elevated [Ca(2+)](cis) (10 microM), both open probability (P(o)) and sensitivity to the drug increased markedly. Caffeine showed a similar tendency. Analysis of lifetimes for single CRC showed that quercetin and caffeine led to different mean open-time and closed-time constants and their proportions. Addition of 10 microM ryanodine to CRC activated by quercetin or caffeine led to the typical subconductance state (approximately 54%) and a subsequent addition of 5 microM ruthenium red completely blocked CRC activity. When 6 microM quercetin and 3 mM caffeine were added together to the cis side of CRC, a time-dependent increase of P(o) was observed (from mode 1 (0.376 +/- 0.043, n = 5) to mode 2 (0.854 +/- 0.062, n = 5)). On the other hand, no further activation was observed when quercetin was added after caffeine. Quercetin affected only the ascending phase of the bell-shaped Ca(2+) activation/inactivation curve, whereas caffeine affected both ascending and descending phases. [(3)H]ryanodine binding to sarcoplasmic reticulum showed that channel activity increased more by both quercetin and caffeine than by caffeine alone. These characteristic differences in the modes of activation of CRC by quercetin and caffeine suggest that the channel activation mechanisms and presumably the binding sites on CRC are different for the two drugs.[1]


  1. Effects of quercetin on single Ca(2+) release channel behavior of skeletal muscle. Lee, E.H., Meissner, G., Kim, d.o. .H. Biophys. J. (2002) [Pubmed]
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