AJP - Cell Physiology, Vol 266, Issue 4 C997-1005, Copyright © 1994 by American Physiological Society
Soluble polycations and cationic amphiphiles inhibit volume-sensitive K-Cl cotransport in human red cell ghosts
J. R. Sachs
Department of Medicine, State University of New York at Stony Brook 11794-8151.
We have measured the effect of soluble polycations (spermine and
methylglyoxal) and cationic amphiphiles (sphingosine and tetracaine) on
K-Cl cotransport in shrunken and swollen red cell ghosts. All substances
inhibited cotransport, and for each agent, the concentration at which
inhibition was half-maximal was about the same for swollen and shrunken
ghosts. Acetylspermine was a much less effective inhibitor than spermine,
which demonstrates that inhibition depends on the cationic groups of
spermine. Spermine was a more effective inhibitor in ATP-free ghosts than
in ghosts containing ATP, which eliminates the possibility that inhibition
of cotransport activity results from inhibition of protein kinase activity.
Inhibition by spermine is as effective in K-free ghosts as in high-K
ghosts; spermine does not inhibit cotransport by reducing the effective K
concentration at the inner membrane surface. We conclude that regulation of
K-Cl cotransport involves negative charges (phosphatidylserine or
phosphatidylinositides) at the inner membrane surface and suggest a model
that accounts for our findings.
