Monitoring of free calcium in the neuronal endoplasmic reticulum: an overview of modern approaches

The concentration of free calcium within the lumen of the endoplasmic reticulum ([Ca2+](L)) fluctuates between 100 and 1000 muM. High [Ca2+](L) provides an electro-driving force for Ca2+ release and supports high Ca2+ diffusion rate within the endoplasmic reticulum lumen. Fluctuations in [Ca2+](L) also regulate numerous chaperones, responsible for postranslational protein processing. Thus, [Ca2+](L), integrates various signalling events and establishes a link between fast signalling, associated with the endoplasmic reticulum Ca2+ release/uptake, and long-lasting adaptive responses relying primarily on the regulation of protein synthesis. This paper overviews modem approaches for the direct monitoring of [Ca2+](L) which rely on three classes of low-affinity Ca2+ probes: ER-targeted aequorin, synthetic fluorescent Ca2+ dyes and GFP-based ER-targeted Ca2+ probes. These techniques, especially as applied to neurones, may substantially widen our appreciation of the endoplasmic reticulum as a universal signalling organelle. (C) 2002 Elsevier Science B.V. All rights reserved.