This review describes recent advances in our understanding of a major Ca2+-entry pathway, the Ca2+ release-activated Ca2+ (CRAC) channel, that is central to mast cell activation.
Animals in which the genes encoding the CRAC channel have been deleted have severely compromised mast cell function and reduced allergic responses. These functional consequences reflect the ability of CRAC channels to activate a range of spatially and temporally distinct responses in mast cells, which contribute to both rapid and slow phases of an allergic response. In addition, the cells can sustain their own activation through positive feedback cycles that involve CRAC channels. Drugs that inhibit CRAC channels are proving effective in treatment of allergic responses both in vitro and in animal models of asthma.
CRAC channels comprise a new therapeutic target for combating allergies including asthma.
aDepartment of Physiology, Anatomy and Genetics, Oxford University, UK
bDepartment of Ear, Nose, and Throat Surgery, John Radcliffe Hospital, Oxford, UK
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