Ischemia-Induced Loss of Epithelial Polarity

Abstract

Proximal tubular cells play a major role in the reabsorption of ions, water and solutes from the glomerular filtrate. This process is accomplished, in large part, by the cells having a polarized surface membrane with structurally, biochemically, and physiologically distinct apical and basolateral membranes separated by cellular junctional complexes. Establishment and maintenance of these unique membrane domains is essential for the normal functioning of proximal tubular cells. Ischemia results in the duration-dependent loss of apical and basolateral surface membrane lipid and protein polarity. This loss of surface membrane polarity is associated with disruption of the microfilament network and opening of cellular tight junctions. Surface membrane lipids and proteins are then free to diffuse laterally within the bilayer into the alternate membrane domain. Functionally, ischemia-induced loss of epithelial polarity is responsible for reduced sodium and glucose reabsorption and for the enhanced susceptibility of proximal tubular cells to aminoglycoside-induced nephrotoxicity. With recovery, proximal tubular cells undergo remodeling of the surface membrane, such that the unique apical and basolateral membrane domains are reestablished, allowing normal cellular function to return.