SLC9A3 and Acidosis: Physiological studies initially concluded that the V-ATPase may mediate up to 40% of proton secretion in this segment (Chan & Giebisch, 1981) and that the V-ATPase is up-regulated in response to metabolic acidosis (Chambrey et al, 1994), but subsequent studies emphasized the critical role of Nhe3 in this process.