CRAC
Calcium-release-activated channel
CRAC channels, also called store-operated calcium channels, are a major source for Ca2+ entry into non-exitable cells. The channels are activated by emptying the intracellular Ca2+ stores. The activation probably involves STIM-1 (stromal interaction molecule), which sens the store depletion and travels to the cell membrane activating the CRAC channel. Stores can be depleted by activating cell-surface receptors that couple to phospholipase C or by dialysing cells with InsP3 and related analogues. Alternatively, pharmacological tools like ionomycin and tharpsigaring can deplete Ca2+-stores. Finally, CRAC channels can also be activated by high (millimolar) concentrations of Ca2+ chelators, which empty the stores. The structure of CRAC channels is unknown. The physiological function is not clearly identified, but seems to involve lymphocyte activation.
Localization:
T-lymphocytes, liver cells, exitable and non-exitable cells
Information link:
http://www.expasy.org/uniprot/Q96D31
QPatch recording of CRAC current:
QPatch whole-cell CRAC current stimulated with a voltage ramp protocol from -100 mV to +100 mV for 100 ms. Upper trace shows the unactivated current, and lower trace shows the CRAC current activated with ionomycin (4 µM extracellularly applied). RBL-2H3 cells were used, which endogenously express CRAC channels.
The I-T plot (below) shows the ionomycin-induced (4µM) CRAC current, blocked in the presence of SKF-96365 (100 µM). Current was measured at -80 mV.
Pharmacological profilling:
Inhibitors: SKF-96365, 2APB
Activators: thapsigargin, InsP3 and related analogues, EGTA, BAPTA
Pathophysiology:
Immune deficiency
QPatch written material:
Application report:
ICRAC recording from RBL-2H3 cells.
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