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説明

Ryanodine is a complex alkaloid natural product and prototypic binder of the Ryanodine Ca²⁺ channel receptors. Ryanodine receptors regulate intracellular movement of Ca²⁺, and the storage and release of Ca²⁺ from the sarcoplasmic reticulum by these receptors has an important role in muscular excitation and contraction. Endogenous regulators of Ca²⁺ release at the Ryanodine receptors require the presence of Ca²⁺ for activation of the channels, in an event known as Ca²⁺-induced Ca²⁺ release. Ryanodine shows very strong and functionally variable binding on these receptors, with a profoundly deleterious effect on the natural flow of Ca²⁺ through the channels. Micromolar concentratrions of Ryanodine have been shown to shut down the channels completely, blocking any flux of ions. At lower nanomolar concentrations, Ryanodine locks the channels in a partially open state, leading to depletion of the Ca²⁺ gradient essential for normal regulation. The toxic effects of Ryanodine are produced by destroying the natural control of Ca²⁺ release from these receptors. Though originally identified through its toxicity to organisms, Ryanodine has proven an invaluable tool in elucidation of Ca²⁺ release and its relationship to excitation and contraction of cells.