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STORE‐OPERATED Ca 2+ CHANNELS AND MICRODOMAINS OF Ca 2+ IN LIVER CELLS
Author(s) -
Barritt Greg J,
Litjens Tom L,
Castro Joel,
Aromataris Edoardo,
Rychkov Grigori Y
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05095.x
Subject(s) - chemistry , radiochemistry , physics
SUMMARY1 Oscillatory increases in the cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyt ) play essential roles in the hormonal regulation of liver cells. Increases in [Ca 2+ ] cyt require Ca 2+ release from the endoplasmic reticulum (ER) and Ca 2+ entry across the plasma membrane. 2 Store‐operated Ca 2+ channels (SOCs), activated by a decrease in Ca 2+ in the ER lumen, are responsible for maintaining adequate ER Ca 2+ . Experiments using patch‐clamp recording and the fluorescent Ca 2+ reporter fura‐2 indicate there is only one type of SOC in rat liver cells. These SOCs have a high selectivity for Ca 2+ and properties essentially indistinguishable from those of Ca 2+ release‐activated Ca 2+ (CRAC) channels. 3 Although Orai1, a CRAC channel pore protein, and stromal interaction molecule 1 (STIM1), a CRAC channel Ca 2+ 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 Ca 2+ 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 Ca 2+ microdomains in the ER and cytoplasmic space are important in both the activation of SOCs and in the signalling actions of Ca 2+ in liver cells. Future experiments will investigate the nature of these microdomains further.