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Department of Medicine and The Liver Center, University of California, San Francisco, California 94143-0538; and Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
Cells involved in
the retrieval and metabolic conversion of amino acids undergo
significant increases in size in response to amino acid uptake. The
resultant adaptive responses to cell swelling are thought to include
increases in membrane K+ and
Cl
permeability through
activation of volume-sensitive ion channels. This viewpoint is largely
based on experimental models of hypotonic swelling, but few mammalian
cells experience hypotonic challenge in vivo. Here we have examined
volume regulatory responses in a physiological model of cell-swelling
alanine uptake in immortalized hepatocytes. Alanine-induced cell
swelling was followed by a decrease in cell volume that was temporally
associated with an increase in membrane
Cl currents. These currents
were dependent both on alanine concentration and
Na+, suggesting that currents were
stimulated by Na+-coupled alanine
uptake. Cl currents were
outwardly rectifying, exhibited an anion permeability sequence of
I > Br > Cl, and were inhibited by
the Cl channel blocker
5-nitro-2-(3-phenylpropylamino)benzoic acid, features similar to those
reported for a widely distributed class of volume-sensitive anion
channels evoked by experimental hypotonic stress. These findings
suggest that volume-sensitive anion channels participate in adaptive
responses to amino acid uptake and provide such channels with a new
physiological context.
amino acids; cell volume; ion channels; liver
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