Knockdown of V-ATPase subunit A (atp6v1a) impairs acid secretion and ion balance in zebrafish (Danio rerio)

In the skin of zebrafish embryo, the vacuolar H⁺-ATPase (V-ATPase, H⁺ pump) distributed mainly in the apical membrane of H⁺-pump-rich cells, which pump internal acid out of the embryo and function similarly to acid-secreting intercalated cells in mammalian kidney. In addition to acid excretion, the electrogenic H⁺ efflux via the H ⁺-ATPases in the gill apical membrane of freshwater fish was proposed to act as a driving force for Na⁺ entry through the apical Na ⁺ channels. However, convincing molecular physiological evidence in vivo for this model is still lacking. In this study, we used morpholino-modified antisense oligonucleotides to knockdown the gene product of H ⁺-ATPase subunit A (atp6v1a) and examined the phenotype of the mutants. The H⁺-ATPase knockdown embryos revealed several abnormalities, including suppression of acid-secretion from skin, growth retardation, trunk deformation, and loss of internal Ca²⁺ and Na ⁺. This finding reveals the critical role of H⁺-ATPase in embryonic acid-secretion and ion balance, as well.