The mechanism of capacitative calcium entry is one of themajor unsolved questions in the field of calcium signalling.Cells derive their signal Ca2+from two separate sources. Itcan be released from an internal reservoir, the endoplasmicreticulum (ER), but once this is depleted Ca2’ is drawn infrom the outside. Jim Putney was one of the first to recognizethat the signal to recruit external Ca” comes from the ERand he coined the term capacitive calcium entry (CCE). Byanalogy with an electrical capacitor, the fully charged ER isquiescent but, once it loses its Ca”, it sends a message tochannels in the membrane to induce a Calcium-Release-Activated-Calcium current (ICRAC).It is highly appropriate forPutney to have written this book because he has been at thecentre of research into this puzzling phenomenon. Althoughsomewhat subjective at times, Putney has written a wonder-fully detailed account of how CCE was discovered. He thengoes on to define the main properties of this entrymechanism which clearly establishes the physiologicalcontext in which the missing messenger must operate. Hisbook could be compared to an Agatha Christie detectivenovel and retitled ‘The Search for the Missing Messenger’.Like all good detective stories, Putney begins by setting thescene with a detailed analysis of the key players. In responseto external stimuli, such as hormones, cells generate themessenger inositol trisphosphate ( InsP,) which diffuses to theER where it binds to InsP, receptors which have the channelsthat release stored Ca”. Once the stores empty, the CCEmechanism kicks in when the ER transmits a signal thattravels back to activate entry channels in the plasmamembrane. Here is where the mystery begins because wedon’t know the messenger mechanism. Even the target of thismessenger, the CRAC channels in the membrane, areunknown. There is no shortage of suspects because many ofthe workers in this field, including myself, have put forwardtheir favourite candidates.
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