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.
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