Maxi chloride channel (Maxi-Cl)

The Maxi chloride channel, also known as the Maxi-anion channel (MAC), is a high-conductance (300–400 pS) voltage-dependent anion channel found in the plasma membrane of most mammalian cell types (Okada et al., 2019). For decades, its molecular identity remained elusive until recent studies identified the solute carrier organic anion transporter family member 2A1 (SLCO2A1) as its core component (Sabirov et al., 2017). The channel is activated by various stimuli, including cell swelling, hypoxia, and ischemia, playing a pivotal role in cell volume regulation and the release of ATP into the extracellular space (UniProt Q92959). This ATP release serves as a critical purinergic signal in processes such as inflammation, apoptosis, and cardiac protection. In disease contexts, the Maxi-Cl channel is implicated in ischemia-reperfusion injury and certain types of cancer, where its dysregulation affects cell survival and signaling (PubMed: 29042477). Pharmacological modulation of the channel is currently limited to non-specific inhibitors like NPPB and DIDS, which are primarily used in research settings (PubChem). Targeting this channel offers therapeutic potential for treating conditions involving excessive ATP release or impaired prostaglandin transport, though its ubiquitous expression poses significant challenges for drug specificity and safety.

Other names

Maxi-anion channelMACHigh-conductance anion channelSLCO2A1Solute carrier organic anion transporter family member 2A1Prostaglandin transporter

Inhibition of high-conductance anion transport and ATP release from cells under stress conditions.