Role of microfilaments in maintenance of proximal tubule structural and functional integrity

P. S. Kellerman, R. A.F. Clark, C. A. Hoilien, S. L. Linas, B. A. Molitoris

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Abstract

To determine the selective effect of microfilament disruption on both cellular structure and function, microfilament-specific doses of cytochalasin D (10 μM) were used in an isolated perfused kidney system. Structurally, cytochalasin D resulted in extensive disruption of the apical surface with blebbing, vacuolization, and patchy loss and fusion of microvilli. Functionally, cytochalasin D resulted in an initial decrease in glomerular filtration rate (300.8 ± 29.9 vs. 541.6 ± 51 μl · min-1 · g-1, P < 0.05) with subsequent stabilization throughout the duration of the perfusion. In contrast, the tubular reabsorption of sodium decreased significantly in a linear fashion from 97.1 ± 0.7 to 64.3 ± 7.0% over the duration of the perfusion. Similarly, the tubular reabsorption of lithium decreased linearly from 74.8 ± 2.6%, before the addition of cytochalasin, to 33.6 ± 6.8% by the end of the perfusion. Correlation of the decrements in percent tubular reabsorption of sodium and lithium for individual kidneys was 0.87 (P < 0.01), suggesting the effect of microfilament disruption on tubular reabsorption of sodium was localized primarily to the proximal tubule. Because ischemic injury is characterized by time-dependent structural alterations in the apical membrane of proximal tubule cells, we set out to determine whether microfilament disruption occurs during ischemic acute renal failure. Utilizing indirect immunofluorescence with an anti-actin antibody, control kidneys demonstrated intact circumferential apical immunofluorescence representing brush-border and terminal web actin staining. Fifteen minutes of ischemia resulted in multiple large gaps in the terminal web, and 50 min of ischemia caused diffuse redistribution of actin immunofluorescence throughout the cytoplasm. These data indicate that disruption of microfilaments results in proximal tubule apical structural and functional alterations, and microfilaments disruption may play an important role in the pathophysiology of ischemic injury.

Original languageEnglish (US)
Pages (from-to)F279-F285
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume259
Issue number2 28-2
StatePublished - Jan 1 1990

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Keywords

  • actin
  • acute renal failure
  • cytochalasin
  • cytoskeleton

ASJC Scopus subject areas

  • Physiology

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