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

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Abstract

Metabolic acidosis causes a reversal of polarity of HCO3– flux in the cortical collecting duct (CCD). In CCDs incubated in vitro in acid media, β-intercalated (HCO3–-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–/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 β-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 β-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 β-intercalated cells. Hence, the adaptive conversion of β-intercalated cells to α-intercalated cells during acid incubation depends upon ECM-associated hensin.

Authors

George J. Schwartz, Shuichi Tsuruoka, Soundarapandian Vijayakumar, Snezana Petrovic, Ayesa Mian, Qais Al-Awqati