An analysis of the mechanism by which cetiedil inhibits the Gardos phenomenon.

Abstract

Energy depletion in the human erythrocyte causes a rise in intracellular calcium. This in turn accelerates the transmembrane movement of potassium and chloride, resulting in cell dehydration. This process, known as the Gardos phenomenon, is inhibited by cetiedil. The present study examines the mechanism by which cetiedil inhibits the Gardos phenomenon. The ability of cetiedil to retard the initial step in the Gardos phenomenon, a rise in intracellular calcium, was first tested. Cetiedil did not prevent calcium accumulation. Cetiedil's ability to inhibit anion movement was next evaluated, as cetiedil could appear to be blocking K movement when in fact it was preventing the movement of its accompanying anion. No inhibitory effect on anion movement was seen. Since cetiedil prevented neither calcium accumulation nor anion movement, it must inhibit the Gardos phenomenon by preventing the opening of the K-specific gate in the erythrocyte membrane. The fact that cetiedil's effect on the Gardos phenomenon could not be removed with repeated cell washing indicates that this effect is irreversible.