Figure 1. Ionic trafficking and charge balance in neutrophil phagosomes.

NOX (Nox2) transports electrons from the cytoplasm to the phagosomal lumen to reduce molecular O₂ to O₂^‒. The consequent membrane potential build-up is neutralized by cation influx through multiple cation channels or pumps, including Hv1 (VG-H⁺), voltage-gated potassium (VG-K⁺) channels, and the V-ATPase proton pump. Ferric MPO (MPO³⁺) dismutates superoxide anion to H₂O₂, whereas MPO compound I (MPO Cpd I) oxidizes Cl^‒ to produce chlorine bleach (HOCl). Phagosomal chloride acquisition is achieved through the following: 1) the PKA-activated chloride channel (e.g., CFTR channel); 2) ClCs (e.g., ClC3 2Cl^‒/H⁺ antiporter); 3) CaCCs; and 4) CCCs (e.g., KCC).