Mast cell immunologically activated chloride channel (I(Cl,immun))

The Mast cell immunologically activated chloride channel, frequently referred to as I(Cl,immun), is a functional ion channel essential for the allergic secretory response in mast cells (Matthews et al., 1989, J Physiol). It is activated downstream of the high-affinity IgE receptor (FcεRI) cross-linking, facilitating a chloride ion flux that regulates the cell's membrane potential (Duffy et al., 2001, J Allergy Clin Immunol). This regulation is crucial for maintaining the electrochemical driving force for calcium (Ca2+) influx through store-operated calcium channels, a prerequisite for the degranulation and release of pro-inflammatory mediators such as histamine, proteases, and cytokines (He et al., 1997, Br J Pharmacol). Historically, this channel has been identified as the molecular target for mast cell stabilizers like cromolyn sodium and nedocromil, which are used clinically to manage asthma and allergic disorders (PubChem). By inhibiting this chloride conductance, these drugs prevent the ionic shifts required for mast cell activation, thereby attenuating the inflammatory cascade. While its precise molecular identity has been associated with proteins like CLIC1 or LRRC8A, it remains a distinct pharmacological target in the study of type I hypersensitivity (Garg et al., 2014, J Biol Chem).

Other names

Immunologically activated chloride channelMast cell chloride channelMCCCIgE-activated chloride channelChloride intracellular channel 1 (CLIC1)

Inhibition of chloride ion flux to prevent membrane potential changes required for sustained calcium-dependent degranulation.