Dramatic magnesium efflux induced by high potassium in rat thymocytes

When incubated in 150 mM KCl, rat thymocytes exhibited a very important mag nesium efflux (11.4 +/- 0.7 mmoles/liter cells/20 min, n = 29), about 90 ti mes higher than the physiological magnesium efflux catalyzed by the Na-Mg e xchanger (0.126 +/- 0.093 mmoles/liter cells/20 min), Cells remained viable (trypan blue test) and membrane integrity was shown by the absence of an i ncrease in sodium permeability, K+-induced magnesium efflux exhibited the f ollowing properties: (i) it required the presence of external chloride; (ii ) it was fully blocked by DIOA, a selective KCl-cotransporter inhibitor (IC 50 = 35 mu m); and (iii) it was associated to a progressive increase in cel l volume via the DIOA-sensitive K-Cl cotransporter, Such cell swelling seem s to play a causal role, because (i) hypertonic media (+400 mM sucrose) abo lished K+-induced magnesium efflux and (ii) hypotonic Ringer media (205 mOs m) increased both cell volume and magnesium efflux (from a basal value of 0 .35 +/- 0.03 mmoles/liter cells/20 min up to 1.44 +/- 0.24 mmoles/liter cel ls/20 min), even in the presence of DIOA. In conclusion, high potassium ind uced a dramatic release of intracellular magnesium from rat thymocytes, Suc h a phenomenon was, at least in part, caused by cell swelling via the DIOA- sensitive K-Cl cotransporter. The nature of the magnesium transport mechani sm and its role in the transduction signal of K-Cl cotransporter activation by cell swelling deserve further investigation. (C) 2000 Academic Press.