Ryanodine receptors (RyRs), like IP3 receptors, are ER Ca2+ channels that release Ca2+ into the cytosol in response to specific signalling pathways. In muscle and neurons, these channels localize to particular regions of specialized ER in order to generate specific Ca2+ signals; in other cells, such compartmentalization is less evident. To compare the intrinsic properties of RyR subtypes, Vincenzo Sorrentino and co-workers have expressed RyR1 and RyR3 in HEK 293 cells, which lack a specialized form of ER and do not normally express RyRs (see). The authors find that, as expected, both RyR1 and RyR3 generate global ER Ca2+signals in response to the agonist caffeine. Significantly, they also show that RyR3-expressing HEK 293 cells (but not those expressing RyR1) exhibit spontaneous, local Ca2+ transients, which are restricted to a few regions of the ER. This indicates not only that different RyR isoforms can generate distinct Ca2+ signals but that a channel itself, rather than a specific cellular environment, can confer spontaneous local Ca2+ release.
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