The Gardos channel is responsible for CDNB-induced dense sickle cell formation

Archil Shartava, Jonah McIntyre, Arvind K. Shah, Steven Goodman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The red blood cells (RBCs) derived from blood taken from homozygous sickle cell (SS) patients demonstrate densities that are inversely proportional to the intracellular reduced glutathione (GSH) content. Addition of 1 mM 1-chloro-2,4-dinitrobenzene (CDNB) to low-density sickle cells (LDSS), at 4°C, results in a shift of LDSS erythrocytes to high-density sickle cells (HDSS), with corresponding decreases in GSH. We have previously demonstrated that this CDNB effect was due to increased K+ leakage and that dense cell formation could be inhibited by clotrimazole (specific for the Gardos channel) but not DIOA (specific for the K+-Cl- co-transport system) at pH 7.4 (Shartava et al. Am. J. Hematol. 1999;62:19-24). Here we demonstrate that clotrimazole (10 μM) inhibits dense cell formation at pH 7.1 and 6.8, while DIOA (1 mM) has no effect. As pH 6.8 is the optimal pH for the K+-Cl- co-transport system, we can now reasonably conclude that damage to the Gardos channel is responsible for CDNB-induced dense cell formation. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)184-189
Number of pages6
JournalAmerican Journal of Hematology
Volume64
Issue number3
DOIs
StatePublished - Jul 6 2000

Fingerprint

Dinitrochlorobenzene
Clotrimazole
Cell Count
Erythrocytes
Glutathione

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

The Gardos channel is responsible for CDNB-induced dense sickle cell formation. / Shartava, Archil; McIntyre, Jonah; Shah, Arvind K.; Goodman, Steven.

In: American Journal of Hematology, Vol. 64, No. 3, 06.07.2000, p. 184-189.

Research output: Contribution to journalArticle

Shartava, Archil ; McIntyre, Jonah ; Shah, Arvind K. ; Goodman, Steven. / The Gardos channel is responsible for CDNB-induced dense sickle cell formation. In: American Journal of Hematology. 2000 ; Vol. 64, No. 3. pp. 184-189.
@article{c830173a1ab442dd8dd3eb9546be8e57,
title = "The Gardos channel is responsible for CDNB-induced dense sickle cell formation",
abstract = "The red blood cells (RBCs) derived from blood taken from homozygous sickle cell (SS) patients demonstrate densities that are inversely proportional to the intracellular reduced glutathione (GSH) content. Addition of 1 mM 1-chloro-2,4-dinitrobenzene (CDNB) to low-density sickle cells (LDSS), at 4°C, results in a shift of LDSS erythrocytes to high-density sickle cells (HDSS), with corresponding decreases in GSH. We have previously demonstrated that this CDNB effect was due to increased K+ leakage and that dense cell formation could be inhibited by clotrimazole (specific for the Gardos channel) but not DIOA (specific for the K+-Cl- co-transport system) at pH 7.4 (Shartava et al. Am. J. Hematol. 1999;62:19-24). Here we demonstrate that clotrimazole (10 μM) inhibits dense cell formation at pH 7.1 and 6.8, while DIOA (1 mM) has no effect. As pH 6.8 is the optimal pH for the K+-Cl- co-transport system, we can now reasonably conclude that damage to the Gardos channel is responsible for CDNB-induced dense cell formation. (C) 2000 Wiley-Liss, Inc.",
author = "Archil Shartava and Jonah McIntyre and Shah, {Arvind K.} and Steven Goodman",
year = "2000",
month = "7",
day = "6",
doi = "10.1002/1096-8652(200007)64:3<184::AID-AJH8>3.0.CO;2-3",
language = "English (US)",
volume = "64",
pages = "184--189",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - The Gardos channel is responsible for CDNB-induced dense sickle cell formation

AU - Shartava, Archil

AU - McIntyre, Jonah

AU - Shah, Arvind K.

AU - Goodman, Steven

PY - 2000/7/6

Y1 - 2000/7/6

N2 - The red blood cells (RBCs) derived from blood taken from homozygous sickle cell (SS) patients demonstrate densities that are inversely proportional to the intracellular reduced glutathione (GSH) content. Addition of 1 mM 1-chloro-2,4-dinitrobenzene (CDNB) to low-density sickle cells (LDSS), at 4°C, results in a shift of LDSS erythrocytes to high-density sickle cells (HDSS), with corresponding decreases in GSH. We have previously demonstrated that this CDNB effect was due to increased K+ leakage and that dense cell formation could be inhibited by clotrimazole (specific for the Gardos channel) but not DIOA (specific for the K+-Cl- co-transport system) at pH 7.4 (Shartava et al. Am. J. Hematol. 1999;62:19-24). Here we demonstrate that clotrimazole (10 μM) inhibits dense cell formation at pH 7.1 and 6.8, while DIOA (1 mM) has no effect. As pH 6.8 is the optimal pH for the K+-Cl- co-transport system, we can now reasonably conclude that damage to the Gardos channel is responsible for CDNB-induced dense cell formation. (C) 2000 Wiley-Liss, Inc.

AB - The red blood cells (RBCs) derived from blood taken from homozygous sickle cell (SS) patients demonstrate densities that are inversely proportional to the intracellular reduced glutathione (GSH) content. Addition of 1 mM 1-chloro-2,4-dinitrobenzene (CDNB) to low-density sickle cells (LDSS), at 4°C, results in a shift of LDSS erythrocytes to high-density sickle cells (HDSS), with corresponding decreases in GSH. We have previously demonstrated that this CDNB effect was due to increased K+ leakage and that dense cell formation could be inhibited by clotrimazole (specific for the Gardos channel) but not DIOA (specific for the K+-Cl- co-transport system) at pH 7.4 (Shartava et al. Am. J. Hematol. 1999;62:19-24). Here we demonstrate that clotrimazole (10 μM) inhibits dense cell formation at pH 7.1 and 6.8, while DIOA (1 mM) has no effect. As pH 6.8 is the optimal pH for the K+-Cl- co-transport system, we can now reasonably conclude that damage to the Gardos channel is responsible for CDNB-induced dense cell formation. (C) 2000 Wiley-Liss, Inc.

UR - http://www.scopus.com/inward/record.url?scp=0034045460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034045460&partnerID=8YFLogxK

U2 - 10.1002/1096-8652(200007)64:3<184::AID-AJH8>3.0.CO;2-3

DO - 10.1002/1096-8652(200007)64:3<184::AID-AJH8>3.0.CO;2-3

M3 - Article

C2 - 10861814

AN - SCOPUS:0034045460

VL - 64

SP - 184

EP - 189

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 3

ER -