and maintenance of this specialized organization is a dynamic and ATP dependent multistage process involving the formation and maintenance of cell-cell and cell-substratum attachments and the targeted delivery of plasma membrane components to the appropriate domains [5]. These processes are very dependent on the cytoskeleton, in general, and the cytoskeletal membrane interactions mediated through F-actin (see Fig. 13-2, 13-3), in particular.

Ischemia in vivo and cellular ATP depletion in cell culture models ("chemical ischemia") are known to produce characteristic surface membrane structural, biochemical, and functional abnormalities in proximal tubule cells. These alterations occur in a duration-dependent fashion and are illustrated in Figures 13-2 and 13-3 and listed in Figure 13-4. Ischemia-induced alterations in the actin cytoskeleton have been postulated to mediate many of the aforementioned surface membrane changes [2,6,7]. This possible link between ischemia-induced actin cytoskeletal alterations and surface membrane structural and functional abnormalities is suggested by several lines. First, the actin cytoskeleton is known to play fundamental roles in surface membrane formation and stability, junctional complex formation and regulation, Golgi structure and function, and cell-extracellular membrane attachment [2,4,5,8]. Second, proximal tubule cell actin cytoskeleton is extremely sensitive to ischemia and ATP depletion [9,10]. Third, there is a strong correlation between the time course of actin and surface membrane alterations during ischemia or ATP depletion [2,9,10]. Finally, many of the characteristic surface membrane changes

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