Neuronal endoplasmic reticulum acts as a single functional Ca2+ store shared by ryanodine and inositol-1,4,5-trisphosphate receptors as revealed by intra-ER [Ca2+] recordings in single rat sensory neurones.

We addressed the fundamentally important question of functional continuity of endoplasmic reticulum (ER) Ca(2+) store in nerve cells. In cultured rat dorsal root ganglion neurones we measured dynamic changes in free Ca(2+) concentration within the ER lumen ([Ca(2+)](L)) in response to activation of inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs). We found that both receptors co-exist in these neurones and their activation results in Ca(2+) release from the ER as judged by a decrease in [Ca(2+)](L). Depletion of Ca(2+) stores following an inhibition of sarco(endoplasmic)reticulum Ca(2+)-ATPase by thapsigargin or cyclopiazonic acid completely eliminated Ca(2+) release via both InsP(3)Rs and RyRs. Similarly, when the store was depleted by continuous activation of InsP(3)Rs, activation of RyRs (by caffeine or 0.5 microM ryanodine) failed to produce Ca(2+) release, and vice versa, when the stores were depleted by activators of RyRs, the InsP(3)-induced Ca(2+) release disappeared. We conclude that in mammalian neurones InsP(3)Rs and RyRs share the common continuous Ca(2+) pool associated with ER.