The whoosh and trickle of calcium signalling

The importance of phospholipase C catalysed hydrolysis of phosphatidylinositol-(4,5)bisphosphate (PtdIns(4,5)P2) to inositol-(1,4,5)trisphosphate (Ins(1,4,5)P3) and sn-1,2-diacylglycerol in the signal transduction pathways of eukaryote cells, in response to extracellular stimuli, is now widely recognised. Although nearly 60 naturally occurring inositol phosphates have been identified in mammalian cells, mobilisation of Ca2+ from the intracellular stores has been most commonly attributed to the generation of Ins(1,4,5)P3 [1]. However, there is increasing evidence for the presence of ryanodine receptors (RyR) in non-excitable cells and for cADP-ribose (cADPr) as the signalling molecule responsible for Ca2+ release via the RyR. But what is the purpose for the co-existence of these two intracellular Ca2+ channels in non-excitable cells and why are they so heterogeneous in their distribution? These questions were explored at the recent International Symposium Calcium Signalling in Inflammatory Cells. Depletion of the intracellular Ca2+ pools is followed by entry of Ca2+ into the cell across the plasma membrane, but the mechanism(s) underlying this 'capacitative Ca2+ entry' is not well understood. Many potential signalling pathways which may account for capacitative Ca2+ entry have been proposed although none have been unanimously accepted. New developments in the elucidation of the mechanism responsible for capacitative Ca2+ entry and how Ca2+ entry is regulated, together with progress in the characterisation of plasma membrane Ca2+ entry channels were also discussed at this symposium.