The plasma membrane inner leaflet PI(4,5)P₂ is essential for the activation of proton-activated chloride channels.

ABSTRACT: Proton-activated chloride (PAC) channels, ubiquitously expressed in tissues, regulate intracellular Cl^- levels and cell death following acidosis. However, molecular mechanisms and signaling pathways involved in PAC channel modulation are largely unknown. Herein, we determine that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] of the plasma membrane inner leaflet is essential for the proton activation of PAC channels. PI(4,5)P₂ depletion by activating phosphatidylinositol 5-phosphatases or G_q protein-coupled muscarinic receptors substantially inhibits human PAC currents. In excised inside-out patches, PI(4,5)P₂ application to the cytoplasmic side increases the currents. Structural simulation reveals that the putative PI(4,5)P_2</

SUBMITTER: Ko W 

PROVIDER: S-EPMC11324729 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature