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

Metabolic acidosis causes a reversal of polarity of HCO 3 -flux in the cortical collecting duct (CCD).In CCDs incubated in vitro in acid media, -intercalated (HCO 3 --secreting) cells are remodeled to functionally resemble -intercalated (H + -secreting) cells.A similar remodeling of -intercalated cells, in which the polarity of H + pumps and Cl -/HCO 3 -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 HCO 3 -flux that is quantitatively similar to an effect previously observed in acidtreated rabbits in vivo.We followed intracellular pH in the same -intercalated cells before and after acid incubation and found that apical Cl/HCO 3 exchange was abolished following acid incubation.Some cells also developed basolateral Cl -/HCO 3 -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 -intercalated cells.Addition of anti-hensin antibodies prevented the acid-induced changes in apical and basolateral Cl -/HCO 3 -exchange observed in the same cells and the corresponding suppression of HCO 3 -secretion.Acid loading also promoted hensin deposition in the ECM underneath adapting -intercalated cells.Hence, the adaptive conversion of -intercalated cells to -intercalated cells during acid incubation depends upon ECM-associated hensin.