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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1454-1459. Prepublished online as a Blood First Edition Paper on April 26, 2005; DOI 10.1182/blood-2005-01-0368. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0368v1 106/4/1454    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by De Franceschi, L. Articles by Brugnara, C. Search for Related Content PubMed PubMed Citation Articles by De Franceschi, L. Articles by Brugnara, C. Related Collections Red Cells Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis Lucia De Franceschi, Alicia Rivera, Mark D. Fleming, Marek Honczarenko, Luanne L. Peters, Philippe Gascard, Narla Mohandas, and Carlo Brugnara From the Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, Verona, Italy; Departments of Laboratory Medicine and Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA; The Jackson Laboratory, Bar Harbor, ME; Lawrence Berkeley National Laboratory, Berkeley, CA; and New York Blood Center, New York, NY. It has been shown that mice with complete deficiency of all 4.1R protein isoforms (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology (spherocytosis) and decreased membrane stability. Here, we characterized the Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice. Compared with wild-type, the Gardos channel of 4.1-/- erythrocytes showed an increase in Vmax (9.75 ± 1.06 vs 6.08 ± 0.09 mM cell x minute; P < .04) and a decrease in Km (1.01 ± 0.06 vs 1.47 ± 1.02 µM; P < .03), indicating an increased sensitivity to activation by intracellular calcium. In vivo function of the Gardos channel was assessed by the oral administration of clotrimazole, a well-characterized Gardos channel blocker. Clotrimazole treatment resulted in worsening of anemia and hemolysis, with decreased red cell survival and increased numbers of circulating hyperchromic spherocytes and microspherocytes. Clotrimazole induced similar changes in 4.2-/- and band 3+/- mice, indicating that these effects of the Gardos channel are shared in different models of murine spherocytosis. Thus, potassium and water loss through the Gardos channel may play an important protective role in compensating for the reduced surface-membrane area of hereditary spherocytosis (HS) erythrocytes and reducing hemolysis in erythrocytes with cytoskeletal impairments. (Blood. 2005;106:1454-1459) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: From Budapest to Bar Harbor James S. Wiley Blood 2005 106: 1145-1146. [Full Text] [PDF] This article has been cited by other articles: E. M. Pasini, M. Kirkegaard, D. Salerno, P. Mortensen, M. Mann, and A. W. Thomas Deep Coverage Mouse Red Blood Cell Proteome: A First Comparison with the Human Red Blood Cell Mol. Cell. Proteomics, July 1, 2008; 7(7): 1317 - 1330. [Abstract] [Full Text] [PDF] A. Rivera, L. De Franceschi, L. L. Peters, P. Gascard, N. Mohandas, and C. Brugnara Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes Am J Physiol Cell Physiol, November 1, 2006; 291(5): C880 - C886. [Abstract] [Full Text] [PDF]

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