Dramatic magnesium efflux induced by high potassium in rat thymocytes.
When incubated in 150 mM KCl, rat thymocytes exhibited a very important magnesium efflux (11.4 +/- 0.7 mmoles/liter cells/20 min, n = 29), about 90 times higher than the physiological magnesium efflux catalyzed by the Na-Mg exchanger (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 increase in sodium permeability. K(+)-induced magnesium efflux exhibited the following properties: (i) it required the presence of external chloride; (ii) it was fully blocked by DIOA, a selective KCl-cotransporter inhibitor (IC(50) = 35 microm); and (iii) it was associated to a progressive increase in cell volume via the DIOA-sensitive K-Cl cotransporter. Such cell swelling seems to play a causal role, because (i) hypertonic media (+400 mM sucrose) abolished K(+)-induced magnesium efflux and (ii) hypotonic Ringer media (205 mOsm) 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 cells/20 min), even in the presence of DIOA. In conclusion, high potassium induced a dramatic release of intracellular magnesium from rat thymocytes. Such a phenomenon was, at least in part, caused by cell swelling via the DIOA-sensitive K-Cl cotransporter. The nature of the magnesium transport mechanism and its role in the transduction signal of K-Cl cotransporter activation by cell swelling deserve further investigation.
Féray
J C
JC
School of Medicine, INSERM U400, 8 rue du Général Sarrail, Créteil Cédex, 94010, France.
Guerrouache
K
K
Garay
R P
RP
D000818:Animals; D017920:Antiporters / Q000378:metabolism; D002264:Carboxylic Acids / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D066298:In Vitro Techniques; D007192:Indenes / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D027981:Symporters; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D000096922:K Cl- Cotransporters
D017920:Antiporters; D002264:Carboxylic Acids; D002352:Carrier Proteins; D002712:Chlorides; D007192:Indenes; D008274:Magnesium; D011188:Potassium; D012964:Sodium; D027981:Symporters; D000096922:K Cl- Cotransporters; C059990:((dihydroindenyl)oxy)alkanoic acid; C046250:sodium-magnesium antiporter