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

• Published in: The Journal of clinical investigation Vol. 109; no. 1; pp. 89 - 99
• Main Authors: Schwartz, George J., Tsuruoka, Shuichi, Vijayakumar, Soundarapandian, Petrovic, Snezana, Mian, Ayesa, Al-Awqati, Qais
• Format: Journal Article
• Language: English; Japanese
• Published: American Society for Clinical Investigation 01.01.2002
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI13292

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, β-intercalated (HCO 3 – -secreting) cells are remodeled to functionally resemble α-intercalated (H + -secreting) cells. A similar remodeling of β-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 acid-treated rabbits in vivo. We followed intracellular pH in the same β-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 β-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 β-intercalated cells. Hence, the adaptive conversion of β-intercalated cells to α-intercalated cells during acid incubation depends upon ECM-associated hensin.