Ryanodin

Rya.nia., The root and stem of the plant yania speciosa family Flacourtiaceae, native to South America, contain from 0.16—0.2% of iasecticidal components, the most important of which is the alkaloid ryanodine [15662-33-9] C25H250 N (8) (mp 219—220°C). This compound is effective as both a contact and a stomach poison. Ryanodine is soluble ia water, methyl alcohol, and most organic solvents but not ia petroleum oils. It is more stable to the action of air and light than pyrethmm or rotenone and has considerable residual action. Ryania has an oral LD q to the rat of 750 mg/kg. The material has shown considerable promise ia the control of the European com borer and codling moth and is used as a wettable powder of ground stems or as a methanohc extract. Ryanodine uncouples the ATP—ADP actomyosia cycle of striated muscle. 

FIGURE 17.25 The structures of nifedipine and ryanodine. Nifedipine binds with high affinity to the Ca" -release channels of t-tubules. Ryanodine binds with high affinity to the Ca" channels of SR terminal cisternae. 

Despite the recent efforts of Beroza (3), the insecticidal alkaloids of the thunder-god vine (Tripterygium ivilfordii) remain only partially characterized. A structure has been proposed for anhydrory-anodine (VIII), a major degradation product of the active principle (ryanodine) of the commercial insecticide ryania (34), and a structure for the parent compound will be proposed soon by Rapoport and his coworkers (27). This again illustrates the importance of collaboration between physical and biological scientists and the intriguing research which each can reveal to the other. 

Sorcin (soluble resistance-related calcium binding protein) was isolated from multidrug-resistant cells and is expressed in a few mammalian tissues such as skeletal muscle, heart, and brain. In the heart, sorcin interacts with the ryanodine receptor and L-type Ca2+-channels regulating excitation in contraction coupling. 

A regenerative process whereby an intracellular Ca2+ channel (IP3 receptor or Ryanodine receptor) is itself stimulated by Ca2+, allowing thereby Ca2+ to promote its own release from intracellular stores. 

Ca2+ sparks are localized and transient Ca2+ release observed recurrently in muscle cells and skinned fibres. A Ca2+ spark is considered to be the elementary process of Ca2+ release in situ from one to a few ryanodine receptors. 

IP3 Receptor Ryanodine Receptor Non-selective Cations Channels TRP Channels... 

Local and transient Ca2+ increases that propagate throughout the cytosol of individual cells in the form of waves. Ca2+ waves are generated by a positive feedback activation of Ca2+ release from the intracellular Ca2+ stores through ryanodine receptors or inositol IP3 receptors. 

Calsequestrin is the major calcium storage protein of the sarcoplasmic reticulum in skeletal and cardiac muscles. It is highly acidic and has a large capacity for Ca2+. Calsequestrin functions to localize calcium near the junctional face of the terminal cistemae from which calcium can be released into the cytosol via the ryanodine receptor. 

Inwardly Rectifying K+ Channels ATP-dependent K+ Channels Voltage-dependent Ca2+ Channels Ryanodine Receptor Voltage-dependent Na2+ Channels... 

Voltage-dependent Ca2+ Channels Ca2+ Channel Blockers Ryanodine Receptor... 

Malignant hyperthermia (MH) is an autosomal-dominant pharmacogenetic disorder that is triggered by exposure to inhalation of general anesthetics, such as halothane. In susceptible individuals, these drugs can induce tachycardia, a greatly increased body metabolism, muscle contracture and an elevated body temperature (above 40°C) with a rapid rate of increase. Many cases of MH are linked to a gene for type 1 ryanodine receptor (RyRl). 

Ryanodine receptor (RyR) is an intracellular Ca2+ release channel in the sarcoplasmic reticulum (SR) or the endoplasmic reticulum (ER). RyR binds ryanodine (a plant alkaloid, see Drugs) with a high affinity, after which it is named. 

Ryanodine Receptor. Table 1 Three Mammalian RyR isoforms... 

Ryanodine Receptor. Figure 1 Three-dimensional architecture of the RyR1 by cryo-electron microscopy, (a), top view (from the T-tubule) (b), bottom view (from the SR lumen) (c), side view (parallel to the SR membrane). The binding sites of FKBP12, apo-CaM and Ca -CaM are indicated in the side view. Courtesy of Dr. M. Samso (modified from Samso etal. (2005) Nat Struct Mol Biol 12 539-544). 

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