[email protected] (C.W.T.) In brief Rossi et al. define mechanisms for IP 3-evoked quantal Ca2+ release that reconcile response termination with undiminished sensitivity to further IP 3 additions. They show that responses requirevery fewIP 3 receptorsthatrapidly openandtheninactivate,allowinggraded responses despite the ability of IP 3 WebInositol 1,4,5-trisphosphate receptors (IP 3 Rs) are intracellular Ca 2+ channels that are widely expressed in animal cells, where they mediate the release of Ca 2+ from intracellular stores evoked by extracellular stimuli. A diverse array of synthetic agonists of IP 3 Rs has defined structure–activity relationships, but existing antagonists have severe limitations.

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