Plasmodium falciparum-activated chloride channels are defective in erythrocytes from cystic fibrosis patients.
An inwardly rectifying anion channel in malaria-infected red blood cells has been proposed to function as the "new permeation pathway" for parasite nutrient acquisition. As the channel shares several properties with the cystic fibrosis transmembrane conductance regulator (CFTR), we tested their interrelationship by whole-cell current measurements in Plasmodium falciparum-infected and uninfected red blood cells from control and cystic fibrosis (CF) patients. A CFTR-like linear chloride conductance as well as a malaria parasite-induced and a shrinkage-activated endogenous inwardly rectifying chloride conductance with properties identical to the malaria-induced channel were all found to be defective in CF erythrocytes. Surprisingly, the absence of the inwardly rectifying chloride conductance in CF erythrocytes had no gross effect on in vitro parasite growth or new permeation pathway activity, supporting an argument against a close association between the Plasmodium-activated chloride channel and the new permeation pathway. The functional expression of CFTR in red blood cells opens new perspectives to exploit the erythrocyte as a readily available cell type in electrophysiological, diagnostic, and therapeutic studies of CF.
Verloo
Patrick
P
Department of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Kocken
Clemens H M
CH
Van der Wel
Annemarie
A
Tilly
Ben C
BC
Hogema
Boris M
BM
Sinaasappel
Maarten
M
Thomas
Alan W
AW
De Jonge
Hugo R
HR
D000818:Animals; D002712:Chlorides / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000097:blood*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D004594:Electrophysiology; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D008288:Malaria / Q000469:parasitology; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010963:Plasmodium falciparum / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
C505032:CFTR protein, human; D002712:Chlorides; D018076:DNA, Complementary; D004232:Diuretics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002713:Chlorine; D005665:Furosemide