Channelpedia

PubMed 19037656


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav3.1



Title: Disruption of the Gardos channel (KCa3.1) in mice causes subtle erythrocyte macrocytosis and progressive splenomegaly.

Authors: Ivica Grgic, Brajesh P Kaistha, Steffen Paschen, Anuradha Kaistha, Christoph Busch, Han Si, Kernt Köhler, Hans-Peter Elsässer, Joachim Hoyer, Ralf Köhler

Journal, date & volume: Pflugers Arch., 2009 Jun , 458, 291-302

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19037656


Abstract
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 ( approximately 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.