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Updated: May 9, 2026
15:29
Whole-Cell Recording of Calcium Release-Activated Calcium (CRAC) Currents in Human T Lymphocytes
Published on: December 21, 2010
CRACM/Orai ion channel expression and function in human lung mast cells.
Ian Ashmole1, S Mark Duffy, Mark L Leyland
1Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
The Journal of Allergy and Clinical Immunology
|March 14, 2012
Summary
CRACM channels are crucial for calcium influx in human lung mast cells, driving allergic responses. Blocking these channels significantly reduces mediator release and smooth muscle contraction, offering a potential therapeutic target for asthma.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Extracellular calcium influx into human lung mast cells (HLMCs) is vital for releasing mediators and cytokines.
- The specific ion channels responsible for this calcium influx in HLMCs have remained unidentified.
- CRACM/Orai ion channels, known for carrying calcium release-activated calcium currents, are potential candidates.
Purpose of the Study:
- To investigate the expression and function of CRACM channels in human lung mast cells (HLMCs).
Main Methods:
- Examined CRACM mRNA, protein, and functional expression in purified HLMCs and human bronchus.
- Utilized electrophysiology to detect CRACM-like currents.
- Employed specific CRACM channel blockers (GSK-7975A and Synta-66) to assess functional inhibition.
Main Results:
- CRACM1, -2, and -3 mRNA and CRACM1 and -2 proteins were detected in HLMCs.
- A CRACM-like current was observed upon FcεRI-dependent activation and with inositol triphosphate dialysis.
- CRACM channel blockers inhibited FcεRI-dependent calcium influx, mediator release (histamine, leukotriene C4, cytokines), and ex vivo bronchial smooth muscle contraction.
Conclusions:
- The presence and function of CRACM channels in HLMCs suggest their role in FcεRI-dependent secretion.
- CRACM channels are a potential therapeutic target for asthma and related allergic diseases.
- CRACM channel blockers effectively inhibited key allergic response pathways in HLMCs and bronchial tissue.
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