Involvement of protein tyrosine kinase in osmoregulation of Na(+) transport and membrane capacitance in renal A6 cells

J Membr Biol. 2000 May 1;175(1):63-77. doi: 10.1007/s002320001055.


Renal A6 cells have been reported in which hyposmolality stimulates Na(+) transport by increasing the number of conducting amiloride-sensitive 4-pS Na(+) channels at the apical membrane. To study a possible role of protein tyrosine kinase (PTK) in the hyposmolality-induced signaling, we investigated effects of PTK inhibitors on the hyposmolality-induced Na(+) transport in A6 cells. Tyrphostin A23 (a PTK inhibitor) blocked the stimulatory action of hyposmolality on a number of the conducting Na(+) channels. Tyrphostin A23 also abolished macroscopic Na(+) currents (amiloride-sensitive short-circuit current, I(Na)) by decreasing the elevating rate of the hyposmolality-increased I(Na). Genistein (another type of PTK inhibitor) also showed an effect similar to tyrphostin A23. Brefeldin A (BFA), which is an inhibitor of intracellular translocation of protein, blocked the action of hyposmolality on I(Na) by diminishing the elevating rate of the hyposmolality-increased I(Na), mimicking the inhibitory action of PTK inhibitor. Further, hyposmolality increased the activity of PTK. These observations suggest that hyposmolality would stimulate Na(+) transport by translocating the Na(+) channel protein (or regulatory protein) to the apical membrane via a PTK-dependent pathway. Further, hyposmolality also caused an increase in the plasma (apical) membrane capacitance, which was remarkably blocked by treatment with tyrphostin A23 or BFA. These observations also suggest that a PTK-dependent pathway would be involved in the hyposmolality-stimulated membrane fusion in A6 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Epithelial Sodium Channels
  • Kidney / cytology
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Sodium / metabolism
  • Sodium Channel Blockers*
  • Sodium Channels / physiology
  • Tyrosine / metabolism
  • Tyrphostins / pharmacology
  • Water-Electrolyte Balance / drug effects


  • Enzyme Inhibitors
  • Epithelial Sodium Channels
  • Sodium Channel Blockers
  • Sodium Channels
  • Tyrphostins
  • Tyrosine
  • Sodium
  • Protein-Tyrosine Kinases
  • tyrphostin A23