Tetracyclines reduce Na+/K+ pump capacity in Calu-3 human airway cells

Y Ito1, H Kume, K Yamaki

  • 12nd Department of Internal Medicine, School of Medicine, Nagoya University, Tsurumai-cho, Showa-ku, 466, Japan. itoyasu@tsuru.med.nagoya-u.ac.jp

Insights

Tetracyclines applied to the apical side of human airway cells suppress sodium-potassium pump (Na+/K+ pump) activity. This effect reduces sodium extrusion capacity without impacting chloride transport.

Area of Science:

  • Cellular Physiology
  • Pharmacology
  • Respiratory Medicine

Background:

  • The Na+/K+ pump is crucial for maintaining cellular ion balance in airway epithelial cells.
  • Tetracyclines are antibiotics with potential off-target effects on cellular transport mechanisms.

Purpose of the Study:

  • To investigate the impact of tetracyclines on Na+/K+ pump activity in human airway Calu-3 cells.
  • To determine if tetracyclines affect ion transport across the apical or basolateral membranes.

Main Methods:

  • Utilized short-circuit current (Isc) measurements in Calu-3 cells to assess Na+/K+ pump capacity.
  • Applied nystatin (Na+ ionophore) and ouabain (Na+/K+ pump inhibitor) to evaluate pump function.
  • Administered tetracycline, minocycline, and demethylchlortetracycline apically and basolaterally.

Main Results:

  • Tetracyclines applied to the apical membrane significantly reduced the nystatin-induced Isc, indicating suppressed Na+/K+ pump activity.
  • No significant effect on Isc was observed when tetracyclines were applied to the basolateral membrane.
  • Tetracyclines did not affect phlorizin- or DPC-sensitive currents, suggesting specific action on the Na+/K+ pump.

Conclusions:

  • Tetracyclines permeate the apical membrane of airway cells and inhibit Na+/K+ pump function.
  • This inhibition reduces the cell's capacity for sodium extrusion.
  • The observed effect on Na+/K+ pump activity occurs independently of changes in chloride transport.