Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2008 Apr 15;111(8):3918-9.
doi: 10.1182/blood-2008-01-135350.

Gardos pathway to sickle cell therapies?

Clinton H Joiner  1
Affiliations
Comment

Gardos pathway to sickle cell therapies?

Clinton H Joiner. Blood. .

Abstract

In this issue of Blood, Ataga and colleagues report that treatment of sickle cell disease patients with senicapoc, a Gardos channel inhibitor, reduces the number of dehydrated cells, increases hemoglobin levels, and diminishes hemolysis.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: C.H.J. participated as a site investigator in the phase 3 trial of senicapoc, funded by Icagen (Durham, NC)/McNeil (Fort Washington, PA). He has been a paid consultant for Icagen. ■

Figures

None
Transport pathways contributing to sickle cell dehydration. Hemoglobin (Hb) S polymerization activates the sickling-induced pathway, permitting Ca++ entry. Increased cytoplasmic Ca++ activates the Gardos pathway, which mediates rapid K+ efflux, balanced by Cl− exit via a chloride conductance pathway. High Hb S concentration resulting from abnormal regulation of K:Cl cotransport may potentiate Hb S polymerization in reticulocytes. Once initiated, the vicious cycle of sickling and dehydration intensifies and perpetuates itself. KCC indicates K:Cl cotransporter; SIP, sickling-induced pathway; G, Gardos pathway; and CC, Cl conductance pathway.
See this image and copyright information in PMC

Comment on

References

    1. Gardos G. The function of calcium in the potassium permeability of human erythrocytes. Biochim Biophys Acta. 1958;30:653–654. - PubMed
    1. Tosteson D, Shea E, Darling RC. Potassium and sodium in red blood cells in sickle cell anemia. J Clin Invest. 1952;48:406–411. - PMC - PubMed
    1. Joiner C, Rettig RK, Jiang M, Risinger M, Franco PS. Urea stimulation of KCl cotransport induces abnormal volume reduction in sickle reticulocytes. Blood. 2007;109:1728–1735. - PMC - PubMed
    1. Lew VL, Etzion Z, Bookchin RM. Dehydration response of sickle cells to sickling-induced Ca(++) permeabilization. Blood. 2002;99:2578–2585. - PubMed
    1. Brugnara C, de Franceschi L, Alper SL. Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives [see comment]. J Clin Invest. 1993;92:520–526. - PMC - PubMed