Store-operated Ca2+ channels and microdomains of Ca2+ in liver cells

© 2009 Blackwell Publishing1. Oscillatory increases in the cytoplasmic Ca2+ concentration ([Ca2+]cyt) play essential roles in the hormonal regulation of liver cells. Increases in [Ca2+]cyt require Ca2+ release from the endoplasmic reticulum (ER) and Ca2+ entry across the plasma membrane. 2. Store-operated Ca2+ channels (SOCs), activated by a decrease in Ca2+ in the ER lumen, are responsible for maintaining adequate ER Ca2+. Experiments using patch-clamp recording and the fluorescent Ca2+ reporter fura-2 indicate there is only one type of SOC in rat liver cells. These SOCs have a high selectivity for Ca2+ and properties essentially indistinguishable from those of Ca2+ release-activated Ca2+ (CRAC) channels. 3. Although Orai1, a CRAC channel pore protein, and stromal interaction molecule 1 (STIM1), a CRAC channel Ca2+ sensor, are components of liver cell SOCs, the mechanism of activation of SOCs, and in particular the role of subregions of the ER, are not well understood. 4. Recent experiments have used the transient receptor potential vanilloid 1 (TRPV1) non-selective cation channel, ectopically expressed in liver cells, and a choleretic bile acid to deplete Ca2+ from different ER subregions. The results of these studies have provided evidence that only a small component of the ER is required for STIM1 redistribution and the activation of SOCs. 5. It is concluded that different Ca2+ microdomains in the ER and cytoplasmic space are important in both the activation of SOCs and in the signalling actions of Ca2+ in liver cells. Future experiments will investigate the nature of these microdomains further.Greg J Barritt, Tom L Litjens, Joel Castro, Edoardo Aromataris and Grigori Y Rychko