Jones L, Ma L, Castro J, Litjens T, Barritt G J, Rychkov G Y
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia.
Biochim Biophys Acta. 2011 Mar;1808(3):745-51. doi: 10.1016/j.bbamem.2010.12.013. Epub 2010 Dec 20.
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.
在生理情况下，激素诱导细胞内储存的Ca²⁺释放，这一过程是对肌醇1,4,5 -三磷酸（IP₃）与其在细胞内细胞器（主要是内质网）膜上表达的受体结合的反应。这些IP₃受体作为通道，将Ca²⁺释放到细胞质空间，在那里它负责调节许多不同的细胞过程。细胞内Ca²⁺储存的耗尽会导致质膜上储存操纵性Ca²⁺通道的激活，从而补充丢失的Ca²⁺并维持Ca²⁺信号传导。IP₃受体有三种亚型，每种都表现出独特的特性，然而，关于每种亚型在储存操纵性Ca²⁺内流激活中的作用知之甚少。最近的证据表明，至少在某些细胞类型中，内质网不是一个均匀的Ca²⁺储存库，可能存在一个特定的亚区室与储存操纵性Ca²⁺通道的激活，特别是与Ca²⁺释放激活的Ca²⁺（CRAC）通道的激活特别相关。此外，这个亚区室可能只表达某些类型的IP₃受体而不表达其他类型。在这里我们表明，H4IIE肝细胞表达所有三种类型的IP₃受体，但只有1型以及程度较轻的3型，而不是2型，参与CRAC电流（I(CRAC)）的激活，而1型和2型，而不是3型，参与对受体刺激观察到的Ca²⁺释放。呈现的结果表明，在H4IIE大鼠肝细胞中，与I(CRAC)激活相关的细胞内Ca²⁺储存亚区室主要表达1型IP₃受体。
