Activation of the Na+-K+ pump by hyposmolality through tyrosine kinase-dependent Cl- conductance in Xenopus renal epithelial A6 cells

J Physiol. 1999 Jul 15;518 ( Pt 2)(Pt 2):417-32. doi: 10.1111/j.1469-7793.1999.0417p.x.


1. We studied the regulatory mechanism of Na+ transport by hyposmolality in renal epithelial A6 cells. 2. Hyposmolality increased (1) Na+ absorption, which was detected as an amiloride-sensitive short-circuit current (INa), (2) Na+-K+ pump activity, (3) basolateral Cl- conductance (Gb,Cl), and (4) phosphorylation of tyrosine, suggesting an increase in activity of protein tyrosine kinase (PTK). 3. A Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), which abolished Gb, Cl, blocked the INa by inhibiting the Na+-K+ pump without any direct effect on amiloride-sensitive Na+ channels. Diminution of Gb,Cl by Cl- replacement with a less permeable anion, gluconate, also decreased the hyposmolality-increased Na+-K+ pump activity. 4. The PTK inhibitors tyrphostin A23 and genistein induced diminution of the hyposmolality-stimulated Gb,Cl, which was associated with attenuation of the hyposmolality-increased Na+-K+ pump activity. 5. Taken together, these observations suggest that: (1) hyposmolality activates PTK; (2) the activated PTK increases Gb,Cl; and (3) the PTK-increased Gb,Cl stimulates the Na+-K+ pump. 6. This PTK-activated Gb,Cl-mediated signalling of hyposmolality is a novel pathway for stimulation of the Na+-K+ pump.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiloride / pharmacology
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Chloride Channels / physiology*
  • Diuretics / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / metabolism*
  • Hypotonic Solutions
  • Kidney / cytology
  • Kidney / metabolism*
  • Nitrobenzoates / pharmacology
  • Osmolar Concentration
  • Ouabain / pharmacology
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / physiology*
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Tyrosine / metabolism
  • Xenopus laevis


  • Chloride Channels
  • Diuretics
  • Enzyme Inhibitors
  • Hypotonic Solutions
  • Nitrobenzoates
  • 5-nitro-2-(3-phenylpropylamino)benzoic acid
  • Tyrosine
  • Ouabain
  • Amiloride
  • Protein-Tyrosine Kinases
  • Sodium-Potassium-Exchanging ATPase