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Disruption of the Gardos channel (KCa3.1) in mice causes subtle erythrocyte macrocytosis and progressive splenomegaly
Ist Teil von
Pflügers Archiv, 2009-06, Vol.458 (2), p.291-302
Ort / Verlag
Berlin/Heidelberg: Springer-Verlag
Erscheinungsjahr
2009
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Gardos channel, the erythrocyte Ca
2+
-activated K
+
channel (K
Ca
3.1), is considered a major regulator of red blood cell (RBC) volume by mediating efflux of potassium and thus cell dehydration and shrinkage. However, the functional importance of K
Ca
3.1 in RBC in vivo is incompletely understood. Here, we used K
Ca
3.1
−/−
-mice to investigate the consequences of K
Ca
3.1 deficiency for RBC indices, functions, and sequestration. RBCs of K
Ca
3.1
−/−
-mice of all ages were mildly macrocytic but their biconcave appearance being preserved. RBC number, total hemoglobin, and hematocrit were unchanged in the adult K
Ca
3.1
−/−
-mice and increased in the premature K
Ca
3.1
−/−
-mice. Filterability, Ca
2+
-dependent volume decrease and osmotic tolerance of RBCs lacking K
Ca
3.1 were noticeably reduced when compared to RBC of wild-type littermates. Deformability to increasing shear stress was unchanged. Strikingly, K
Ca
3.1
−/−
-mice developed progressive splenomegaly which was considerable (∼200% of controls) in the >6-month-old mice and was paralleled by increased iron deposition in the aged mice presumably as a consequence of enhanced RBC sequestration. Daily injections of the K
Ca
3.1-blocker TRAM-34 (120 mg/kg) also produced mild splenomegaly in wild-type mice. We conclude that genetic deficit of erythroid K
Ca
3.1 causes mild RBC macrocytosis, presumably leading to reduced filterability, and impairs volume regulation. These RBC defects result in mild but progressive splenomegaly.