Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin

Metabolic acidosis causes a reversal of polarity of HCO3- flux in the cortical collecting duct (CCD). In CCDs incubated in vitro in acid media, beta-intercalated (HCO3--secreting) cells are remodeled to functionally resemble cc-intercalated (H+-secreting) cells. A similar remodeling of beta-intercalated cells, in which the polarity of H+ pumps and Cl-/HCO3- exchangers is reversed, occurs in cell culture and requires the deposition of polymerized hensin in the ECM. CCDs maintained 3 h at low pH ex vivo display a reversal of HCO3- flux that is quantitatively similar to an effect previously observed in acid-treated rabbits in vivo. We followed intracellular pH in the same beta-intercalated cells before and after acid incubation and found that apical Cl/HCO3 exchange was abolished following acid incubation. Some cells also developed basolateral Cl-/HCO3- exchange, indicating a reversal of intercalated cell polarity. This adaptation required intact microtubules and microfilaments, as well as new protein synthesis, and was associated with decreased size of the apical surface of beta-intercalated cells. Addition of anti-hensin antibodies prevented the acid-induced changes in apical and basolateral Cl-/HCO3- exchange observed in the same cells and the corresponding suppression of HCO3- secretion. Acid loading also promoted hensin deposition in the ECM underneath adapting beta-intercalated cells. Hence, the adaptive conversion of beta-intercalated cells to alpha-intercalated cells during acid incubation depends upon ECM-associated hensin.