title: Does a decrease in subplasmalemmal Ca2+ explain how store-operated Ca2+ channels are opened?
abstract: The phenomenon of store-activated Ca2+ inflow (capacitative Ca2+ entry) in which the depletion of Ca2+ in the endoplasmic reticulum (ER) increases the probability of opening of store-operated Ca2+ channels (SOCs) located in the plasma membrane is ubiquitous in 'non-excitable' animal cells and is also found in some 'excitable' cells. At present, neither the structures of SOCs nor the mechanism(s) by which a decrease in Ca2+ in the lumen of the ER activates SOCs are well understood. This paper discusses the hypothesis that a decrease in the concentration of Ca2+ in restricted regions of the subplasmalemmal space (bounded by the plasma membrane and peripheral regions of the ER) is responsible for the activation of SOCs. The hypothesis rests on observations made by others that Ca2+ is a strong feed-back inhibitor of SOCs and of the endoplasmic reticulum (Ca(2+)+Mg2+)-ATPases (SERCAs), and on the concepts (developed previously by others) of a subplasmalemmal space and the directed flow of Ca2+ through SOCs into the lumen of the ER and from there to the deep cytoplasmic space. The way in which the hypothesis might explain the actions of agonists (acting via inositol 1,4,5-trisphosphate) and thapsigargin (an inhibitor of SERCAs) in activating SOCs under physiological conditions is described. The proposed involvement of thapsigargin-insensitive SERCAs, and possible limitations of the hypothesis are discussed.
authors.affiliation: Department of Medical Biochemistry, School of Medicine, Faculty of Health Sciences, Flinders University, Adelaide, Australia. Greg.Barritt@flinders.edu.au
authors.forename: G J
authors.initials: GJ
authors.lastname: Barritt
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D012508:Sarcolemma / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D002118:Calcium