The predominant role of IP3 type 1 receptors in activation of store-operated Ca2+ entry in liver cells

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. (c) 2010 Elsevier B.V. All rights reserved.