Calcium dependence of integrity of the actin cytoskeleton of proximal tubule cell microvilli

Keizo Sogabe, Nancy F. Roeser, Julie A. Davis, Saul Nurko, Manjeri A. Venkatachalam, Joel M. Weinberg

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Abstract

To better define the role of Ca2+ in pathophysiological alterations of the proximal tubule microvillus actin cytoskeleton, we studied freshly isolated tubules in which intracellular free Ca2+ was equilibrated with highly buffered, precisely defined medium Ca2+ levels using a combination of the metabolic inhibitor, antimycin, and the ionophore, ionomycin, in the presence of glycine, to prevent lethal membrane damage and resulting nonspecific changes. Increases of Ca2+ to ≥ 10 μM were sufficient to initiate concurrent actin depolymerization, fragmentation of F-actin into forms requiring high-speed centrifugation for recovery, redistribution of villin to sedimentable fractions, and structural microvillar damage consisting of severe swelling and fragmentation of actin cores. These observations implicate Ca2+-dependent, villin-mediated actin cytoskeletal disruption in tubule cell microvillar damage under conditions conceivably present during pathophysiological states. However, despite prior evidence for cytosolic free Ca2+ increases of the same order of magnitude and similar structural microvillar alterations, Ca2+- and villin-mediated events did not appear to account for the initial microvillar damage that occurs during ATP depletion induced by antimycin alone or hypoxia.

Original languageEnglish (US)
Pages (from-to)F292-F303
JournalAmerican Journal of Physiology
Volume271
Issue number2 PART 2
StatePublished - Dec 1 1996

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Keywords

  • Acute renal failure
  • Fodrin
  • Glycine
  • Hypoxia
  • Kidney
  • Rabbit
  • Villin

ASJC Scopus subject areas

  • Physiology (medical)

Cite this

Sogabe, K., Roeser, N. F., Davis, J. A., Nurko, S., Venkatachalam, M. A., & Weinberg, J. M. (1996). Calcium dependence of integrity of the actin cytoskeleton of proximal tubule cell microvilli. American Journal of Physiology, 271(2 PART 2), F292-F303.