THE WHOOSH AND TRICKLE OF CALCIUM SIGNALING

The importance of phospholipase C catalysed hydrolysis of phosphatidyl inositol-(4,5)bisphosphate (Ptdlns(4,5)P-2) to inositol-(1,4,5)trispho sphate (Ins(1,4,5)P-3) and sn-1,2-diacylglycerol in the signal transdu ction pathways of eukaryote cells, in response to extracellular stimul i, is now widely recognised. Although nearly 60 naturally occurring in ositol phosphates have been identified in mammalian cells, mobilisatio n of Ca2+ from the intracellular stores has been most commonly attribu ted to the generation of Ins(1,4,5)P-3 [1]. However, there is increasi ng evidence for the presence of ryanodine receptors (RyR) in non-excit able cells and for cADP-ribose (cADPr) as the signalling molecule resp onsible 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 Ca2pools is followed by entry of Ca2+ into the cell across the plasma mem brane, but the mechanism(s) underlying this 'capacitative Ca2+ entry' is not well understood. Many potential signalling pathways which may a ccount for capacitative Ca2+ entry have been proposed although none ha ve been unanimously accepted. New developments in the elucidation of t he mechanism responsible for capacitative Ca2+ entry and how Ca2+ entr y is regulated, together with progress in the characterisation of plas ma membrane Ca2+ entry channels were also discussed at this symposium.