Ryanodine
- 貨號 Cat. No.
- R-500
- 規格 Size
- 1 mg 5x1mg
Description
Ryanodine
| Product#: | R-500 |
| Sizes: |
| 1 mg |
| 5 x 1 mg |
| M.W.: | 493.5 |
| Structure: |
 |
| Purity: | >98% |
| Bioassay: |
| Ryanodine inhibits caffeine-induced Ryanodine receptor activation. |
 |
| The graph demonstrates Ca2+ flow from the ER to the cytosol in flou-3 AM-loaded cardiomyocite cells, which stimulated with 2 mM caffeine in the presence (purple) or absence (blue) of 25 然 Ryanodine (#R-500). Time of stimulation with caffeine is represented by the arrow. Extracellular Ca2+ was absorbed with EGTA. |
| References: |
1. | Elison, C. and Jenden, D.J. (1967) Biochem. Pharmacol. 16, 1347. |
2. | Frank, M. and Sleaton, W.W. (1975) Res. Commun. Chem. Pathol. Pharmacol. 11, 65. |
3. | Campbell, K.P. et al. (1987) J. Biol. Chem. 262, 6460. |
4. | Lai, F.A. et al. (1989) J. Biol. Chem. 264, 16776. |
5. | Hymel, L. et al. (1988) Proc. Natl. Acad. Sci. USA 85, 441. |
6. | Lai, F.A. et al. (1988) Nature 331, 315. |
7. | Smith, J.S. et al. (1988) J. Gen. Physiol. 92, 1. |
8. | Tu, Q. et al. (1994) Biophys. J. 67, 2280. |
9. | Ogawa, Y. (1994) Crit. Rev. Biochem. Mol. Biol. 29, 229. |
10. | Rousseau, E. et al. (1987) Am. J. Physiol. Cell. Physiol. 253, C364. |
11. | Buck, E. (1992) J. Biol. Chem. 267, 23560. |
12. | Ogawa, Y. (1994) Crit. Rev. Biochem. Mol. Biol. 29, 229. |
13. | Chu, A. et al. (1990) Mol Pharmacol. 37, 735. |
Ryanodine is foundnaturally in the stem and roots of the plant Ryania speciosa.The Ryanodine alkaloid was first isolated as a potential insecticide1 but was found to act as potent paralytic on skeletal andcardiac muscles.2 Ryanodine inhibits SR Ca2+ release by binding with high affinity to the Ryanodine receptor (RyR) channel as a tetrameric complex.3,4
The RyR channel has three isoforms and is a poorly selectiveCa2+ channel (selectivity Ca2+/K+ ~6) with very high conductance (~700 pS with K+ as charge carrier and ~100 pS with Ca2+ as charge carrier). The channel is regulated by Ca2+, Mg2+, ATP, and caffeine. Application of Ryanodinelocks the channel in a slow-gating subconductance state. Opening of the Ryanodine-bound channelis long-lived and gives rise to a smaller unit current than (~1/3 or ~1/2) the control amplitude. This action of Ryanodine on single RyR channelfunction is quite distinctive and is often used for functionalidentification of thechannel.5-8
Ryanodine binds with high affinity to RyR proteins in a pore located in the carboxyl terminus of the protein.9 Binding induces a complex change in singleRyR channel function. This change is similar in all three RyRchannel isoforms, inducing open events of very long durationand simultaneous reduction of ion conductance throughthe pore.10,7 This dual impact on single-channelfunction (i.e., slower gating and reduced conductance) suggests acomplicated mode of action. This is also supported by the rathercomplicated Ryanodine dose dependency. Low doses of Ryanodine(~10 nM) are reported to increase the frequency of single RyRchannel openings to the normal conductance level. IntermediateRyanodine doses (~1 然) are reported to induce the classical Ryanodineaction described above. High doses of Ryanodine(~100 然) are reported to lock the channel in a closed configuration.11,10
It is generally assumed that eachRyR monomer contains one high-affinity Ryanodine binding site (KD <50 nM).6,12 It is sugested that cooperativeinteraction between RyR monomers iswhat generates the complexity.13 This is supported by Ryanodinebinding studies, which suggest the existence of additional lower affinity Ryanodine binding sites.6,13