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Am J Physiol Cell Physiol 275: C416-C422, 1998;
0363-6143/98 $5.00
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Vol. 275, Issue 2, C416-C422, August 1998

Intracellular ionic strength regulates the volume sensitivity of a swelling-activated anion channel

Carolyn L. Cannon1,2, Srisaila Basavappa1, and Kevin Strange1

1 Laboratory of Cellular and Molecular Physiology, Departments of Anesthesiology and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232; and 2 Division of Respiratory Diseases, Children's Hospital, Boston, Massachusetts 02115

Cell swelling activates an outwardly rectifying anion channel termed VSOAC (volume-sensitive organic osmolyte/anion channel). Regulation of VSOAC by intracellular electrolytes was characterized in Chinese hamster ovary cells by whole cell patch clamp. Elevation of intracellular CsCl concentration from 40 to 180 mM resulted in a concentration-dependent decrease in channel activation. Activation of VSOAC was insensitive to the salt gradient across the plasma membrane, the intracellular concentration of specific anions or cations, and the total intracellular concentration of cations, anions, or electrolytes. Comparison of cells dialyzed with either CsCl or Na2SO4 solutions demonstrated directly that VSOAC activation is modulated by intracellular ionic strength (µi). The relative cell volume at which VSOAC current activation was triggered, termed the channel volume set point, decreased with decreasing ionic strength. At µi = 0.04, VSOAC activation occurred spontaneously in shrunken cells. The rate of VSOAC activation was nearly 50-fold higher in cells with µi = 0.04 vs. those with µi = 0.18. We propose that µi modulates the volume sensor responsible for channel activation.

chloride channels; volume regulation; cell swelling; patch clamp; organic osmolytes


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