Plasticity of intercalated cell polarity: effect of metabolic acidosis

The cortical collecting duct (CCD) is capable of secreting H(+) or HCO3(-) depending on the acid-base status in vivo. Transport is a function of two types of intercalated cells in the CCD: A-intercalated cells secrete H(+) and B-intercalated cells secrete HCO3(-). Metabolic acidosis results in a decrease in HCO3(-) secretion and an increase in H(+) secretion by the respective cells. Using a model of metabolic acidosis in vitro, we have shown that the down-regulation of HCO3(-) secretion occurs by endocytosis of apical anion exchangers in B-intercalated cells. The finding of basolateral anion exchangers in some adapted B-intercalated cells is consistent with a reversal of functional epithelial polarity. Plasticity of polarity is also observed in cultured intercalated cells: high-density plating results in converting B- to A-intercalated cells via the deposition of the novel protein hensin in the extracellular matrix. A key problem in renal physiology is to investigate the role of hensin in mediating the adaptation of the CCD to acidosis in vitro and in vivo.