Abstract
PAC channel is an evolutionarily conserved pH-gated chloride ion channel. Its activity at the plasma membrane is widely observed across different tissues. Under pathological conditions associated with acidosis, such as ischemic stroke, PAC at the cell surface is activated by a drop in tissue pH, allowing the entry of chloride into the cells, which in turn causes cell swelling and contributes to acid-induced brain injury. PAC also traffics to endosomes, where it regulates lumen acidification. Threshold for PAC activation depends on its subcellular localization, so we hypothesized that PAC channel is regulated by phosphatidylinositol PI(4,5)P2 lipid that is exclusively present in the plasma membrane.
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