▪ Abstract This review focuses on the structure and function of the branchial chloride cell in freshwater fishes. The mitochondria-rich chloride cell is believed to be the principal site of trans-epithelial Ca²⁺ and Cl⁻ influxes. Though currently debated, there is accruing evidence that the pavement cell is the site of Na⁺ uptake via channels linked electrically to an apical membrane vacuolar H⁺-ATPase (proton pump).

Chloride cells perform an integral role in acid-base regulation. During conditions of alkalosis, the surface area of exposed chloride cells is increased, which serves to enhance base equivalent excretion as the rate of Cl⁻/HCO₃⁻ exchange is increased. Conversely, during acidosis, the chloride cell surface area is diminished by an expansion of the adjacent pavement cells. This response reduces the number of functional Cl⁻/HCO₃⁻ exchangers.

Under certain conditions that challenge ion regulation, chloride cells proliferate on the lamellae. This response, while optimizing the Ca²⁺ and Cl⁻ transport capacity of the gill, causes a thickening of the blood-to-water diffusion barrier and thus impedes respiratory gas transfer.