Molecular pharmacology of store-operated CRAC channels

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Calcium influx through store-operated Ca2+ release-activated Ca2+ channels (CRAC channels) is a well-defined mechanism of generating cellular Ca2+ elevations that regulates many functions including gene expression, exocytosis and cell proliferation. The identifications of the ER Ca2+ sensing proteins, STIM1-2 and the CRAC channel proteins, Orai1-3, have led to improved understanding of the physiological roles and the activation mechanism of CRAC channels. Defects in CRAC channel function are associated with serious human diseases such as immunodeficiency and auto-immunity. In this review, we discuss several pharmacological modulators of CRAC channels, focusing specifically on the molecular mechanism of drug action and their utility in illuminating the mechanism of CRAC channel operation and their physiological roles in different cells.

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