A high specificity and affinity interaction with serum albumin stimulates an anion conductance in malaria-infected erythrocytes.
The intraerythrocytic development of P. falciparum induces New Permeability Pathways (NPP) in the membrane of the parasitized erythrocyte which provide the parasite with nutrients, adjust the erythrocyte electrolyte composition to the needs of the parasite, and dispose of metabolic waste products and osmolytes. Patch-clamp recordings identified inwardly and outwardly rectifying (OR) anion conductances in the host erythrocyte membrane as electrophysiological correlate of the NPP. The OR conductance is regulated by serum. Here we show that serum albumin (SA) stimulated OR-generated Cl(-) and lactate outward currents with an EC(50) of approximately 100 nM while other proteins such as ovalbumin or casein did not. The stimulatory efficacy did not differ between fatty acid free bovine SA and recombinant human SA and disruption of the SA tertiary structure abolished the effect suggesting that intact SA protein and not other bound factors interact with the erythrocyte membrane. Taken together, the data indicate a high affinity and specificity interaction of native SA with the parasitized erythrocytes which might underlie the observed dependence of P. falciparum growth in vitro on SA.
Duranton
Christophe
C
Department of Physiology, University of Tübingen, Tübingen, Tübingen, Germany.
Tanneur
Valerie
V
Lang
Camelia
C
Brand
Verena B
VB
Koka
Saisudha
S
Kasinathan
Ravi S
RS
Dorsch
Martina
M
Hedrich
Hans J
HJ
Baumeister
Stefan
S
Lingelbach
Klaus
K
Lang
Florian
F
Huber
Stephan M
SM
D000818:Animals; D002364:Caseins / Q000494:pharmacology; D018118:Chloride Channels / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D019344:Lactic Acid / Q000378:metabolism; D008288:Malaria / Q000378:metabolism*; D010047:Ovalbumin / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D002364:Caseins; D018118:Chloride Channels; D011994:Recombinant Proteins; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D010047:Ovalbumin