The Journal of Membrane Biology

, Volume 102, Issue 1, pp 11–19 | Cite as

Silver ion (Ag+)-Induced increases in cell membrane K+ and Na+ permeability in the renal proximal tubule: Reversal by thiol reagents

  • Bruce C. Kone
  • Melissa Kaleta
  • Steven R. Gullans


The initial mechanisms of injury to the proximal tubule following exposure to nephrotoxic heavy metals are not well established. We studied the immediate effects of silver (Ag+) on K+ transport and respiration with extracellular K+ and O2 electrodes in suspensions of renal cortical tubules. Addition of silver nitrate (AgNO3) to tubules suspended in bicarbonate Ringer's solution caused a rapid, dose-dependent net K+ efflux (K m =10−4m,Vmax=379 nmol K+/min/mg protein) which was not inhibited by furosemide, barium chloride, quinine, tetraethylammonium, or tolbutamide. An increase in the ouabain-sensitive oxygen consumption rate (QO2) (13.9±1.1 to 25.7±4.4 nmol O2/min/mg,P<0.001), was observed 19 sec after the K+ efflux induced by AgNO3 (10−4m), suggesting a delayed increase in Na+ entry into the cell. Ouabain-insensitive QO2, nystatin-stimulated QO2, and CCCP-uncoupled QO2 were not significantly affected, indicating preserved function of the Na+, K+-ATPase and mitochondria. External addition of the thiol reagents dithiothreitol (1mm) and reduced glutathione (1mm) prevented and/or immediately reversed the effects on K+ transport and QO2. We conclude that Ag+ causes early changes in the permeability of the cell membrane to K+ and then to Na+ at concentrations that do not limit Na+, K+-ATPase activity or mitochondrial function. These alterations are likely the result of a reversible interaction of Ag+ with sulfhydryl groups of cell membrane proteins and may represent initial cytotoxic effects common to other sulfhydryl-reactive heavy metals on the proximal tubule.

Key Words

silver ion epithelial transport K+ channels sulfhydryl groups oxygen consumption proximal tubule glutathione 


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Copyright information

© Springer-Verlag New York Inc. 1988

Authors and Affiliations

  • Bruce C. Kone
    • 1
  • Melissa Kaleta
    • 1
  • Steven R. Gullans
    • 1
  1. 1.Renal Division, Department of MedicineBrigham and Women's Hospital and Harvard Medical SchoolBoston

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