title: The predominant role of IP₃ type 1 receptors in activation of store-operated Ca²+ entry in liver cells.
abstract: Physiologically, hormone induced release of Ca²+ from intracellular stores occurs in response to inositol 1,4,5-trisphosphate (IP₃) binding to its receptors expressed on the membranes of intracellular organelles, mainly endoplasmic reticulum. These IP₃ receptors act as channels, releasing Ca²+ into the cytoplasmic space where it is responsible for regulating a host of distinct cellular processes. The depletion of intracellular Ca²+ stores leads to activation of store-operated Ca²+ channels on the plasma membrane which replenishes lost Ca²+ and sustain Ca²+ signalling. There are three isoforms of IP₃ receptor, each exhibiting distinctive properties, however, little is known about the role of each isoform in the activation of store-operated Ca²+ entry. Recent evidence suggest that at least in some cell types the endoplasmic reticulum is not a homogeneous Ca²+ store, and there might be a sub-compartment specifically linked to the activation of store-operated Ca²+ channels, and Ca²+ release activated Ca²+ (CRAC) channel in particular. Furthermore, this sub-compartment might express only certain types of IP₃ receptor but not the others. Here we show that H4IIE liver cells express all three types of IP₃ receptor, but only type 1 and to a lesser extent type 3, but not type 2, participate in the activation of CRAC current (I(CRAC)), while type 1 and type 2, but not type 3, participate in observed Ca²+ release in response to receptor stimulation. Presented results suggest that in H4IIE rat liver cells the sub-compartment of intracellular Ca²+ store linked to the activation of I(CRAC) predominantly expresses type 1 IP₃ receptors.
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Jones
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: J
authors.initials: J
authors.lastname: Castro
authors.forename: T
authors.initials: T
authors.lastname: Litjens
authors.forename: G J
authors.initials: GJ
authors.lastname: Barritt
authors.forename: G Y
authors.initials: GY
authors.lastname: Rychkov
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium