Epithelial polarity following ischemia: a requirement for normal cell function.
Ischemic injury results in proximal tubule (PT) dysfunction and loss of surface membrane (SM) polarity. Since epithelial vectorial transport requires SM polarity, we set out to determine if correction of renal cortical PT dysfunction following ischemia was dependent on the reestablishment of SM polarity. Acute renal failure was induced using a bilateral 50-min pedicle clamp. Serum creatinine and fractional sodium excretion were maximal on day 1, remained elevated on day 3, and returned toward base line by day 8. PT cellular ultrastructure was normal by day 3. Despite rapid morphological recovery, ischemia resulted in a prolonged defect in glucose reabsorption. The delayed recovery of normal glucose handling closely paralleled the slow normalization of apical membrane lipid polarity. Na+-K+-ATPase polarity was also lost secondary to ischemia as demonstrated cytochemically and biochemically by the redistribution of Na+-K+-ATPase to the apical membrane. The time required to reestablish normal Na+-K+-ATPase polarity (8 days) paralleled the recovery of normal PT Na+ reabsorption (8 days), as assessed by fractional lithium clearances. This finding supports the hypothesis that apical Na+-K+-ATPase is in part responsible for reduced Na+ reabsorption following ischemic injury. In summary, these data suggest that functional recovery of PT glucose and Na+ reabsorption following a reversible ischemic insult requires not only morphological recovery, but also the reestablishment of surface membrane lipid and protein polarity.
Spiegel
D M
DM
Division of Nephrology, Veterans Administration Medical Center, Denver, Colorado.
Wilson
P D
PD
Molitoris
B A
BA
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004848:Epithelium / Q000473:pathology / Q000502:physiology; D006651:Histocytochemistry; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008563:Membrane Lipids / Q000502:physiology; D008871:Microvilli / Q000502:physiology; D008954:Models, Biological; D010743:Phospholipids / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D008563:Membrane Lipids; D010743:Phospholipids; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase