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Biomedical subjects

Christophe Duranton

Publications and source records attributed to Christophe Duranton.

6 recordsLinked to original sources
PubMed2003

Modulation of whole-cell currents in Plasmodium falciparum-infected human red blood cells by holding potential and serum.

Recent electrophysiological studies have identified novel ion channel activity in the host plasma membrane of Plasmodium falciparum-infected human red blood cells (RBCs). However, conflicting data have been published with regard to the characteristics of induced channel activity measured in the whole-cell configuration of the patch-clamp technique. In an effort to establish the reasons for these discrepancies, we demonstrate here two factors that have been found to modulate whole-cell recordings in malaria-infected RBCs. Firstly, negative holding potentials reduced inward currents (i.e. at negative potentials), although this result was highly complex. Secondly, the addition of human serum increased outward currents (i.e. at positive potentials) by approximately 4-fold and inward currents by approximately 2-fold. These two effects may help to resolve the conflicting data in the literature, although further investigation is required to understand the underlying mechanisms and their physiological relevance in detail.

Animals↗
PubMed2003

Cation channels, cell volume and the death of an erythrocyte.

Similar to a variety of nucleated cells, human erythrocytes activate a non-selective cation channel upon osmotic cell shrinkage. Further stimuli of channel activation include oxidative stress, energy depletion and extracellular removal of Cl-. The channel is permeable to Ca2+ and opening of the channel increases cytosolic [Ca2+]. Intriguing evidence points to a role of this channel in the elimination of erythrocytes by apoptosis. Ca2+ entering through the cation channel stimulates a scramblase, leading to breakdown of cell membrane phosphatidylserine asymmetry, and stimulates Ca(2+)-sensitive K+ channels, thus leading to KCl loss and (further) cell shrinkage. The breakdown of phosphatidylserine asymmetry is evidenced by annexin binding, a typical feature of apoptotic cells. The effects of osmotic shock, oxidative stress and energy depletion on annexin binding are mimicked by the Ca2+ ionophore ionomycin (1 microM) and blunted in the nominal absence of extracellular Ca2+. Nevertheless, the residual annexin binding points to additional mechanisms involved in the triggering of the scramblase. The exposure of phosphatidylserine at the extracellular face of the cell membrane stimulates phagocytes to engulf the apoptotic erythrocytes. Thus, sustained activation of the cation channels eventually leads to clearance of affected erythrocytes from peripheral blood. Susceptibility to annexin binding is enhanced in several genetic disorders affecting erythrocyte function, such as thalassaemia, sickle-cell disease and glucose-6-phosphate dehydrogenase deficiency. The enhanced vulnerability presumably contributes to the shortened life span of the affected erythrocytes. Beyond their role in the limitation of erythrocyte survival, cation channels may contribute to the triggering of apoptosis in nucleated cells exposed to osmotic shock and/or oxidative stress.

Animals↗
PubMed2003

Electrophysiological properties of the Plasmodium Falciparum-induced cation conductance of human erythrocytes.

Intraerythrocyte survival of the malaria pathogen Plasmodium Falciparum depends on the induction of the new-permeability-pathways (NPPs) in the host cell membrane. NPPs are characterized as anion- and organic osmolyte-permeable channels which also exhibit a low but significant permeability for inorganic cations. To disclose the electrophyiologial properties of this infection-induced cation permeability whole-cell currents were recorded in Plasmodium Falciparum-infected human erythrocytes (pRBC) using bath and pipette solutions with low Cl(-) concentrations. The data disclose a nonselective cation conductance (G(CAT)) which activated upon removal of extracellular Cl(-). Upon activation, G(CAT) was 0.3 +/- 0.05 nS (n=16) in control RBC and 2.0 +/- 0.3 nS (n = 32) in pRBC indicating an induction of G(CAT) during the infection. G(CAT) of pRBC exibited a relative permselectivity for monovalent cations of Cs(+)ñK(+)>Na(+)>Li(+) (P(Na)/P(K) ñ 0.5) with a significant permeability for Ca(2+). G(CAT) of pRBC was inhibited by NPPs blockers (furosemide and NPPB) and cation channel blockers (amiloride, EIPA, GdCl(3)) with the highest sensitivity to EIPA (IC(50)-0.5 microM). Most importantly, the blocker sensitivities differed between the infection-induced anion conductances and G(CAT) suggesting that G(CAT) and the anion conductances represent different channel proteins which in concert build up the NPPs.

Amiloride↗
PubMed2002

Oxidation induces a Cl(-)-dependent cation conductance in human red blood cells.

Oxidative stress induces complex alterations of membrane proteins in red blood cells (RBCs) eventually leading to haemolysis. To study changes of membrane ion permeability induced by oxidative stress, whole-cell patch-clamp recordings and haemolysis experiments were performed in control and oxidised human RBCs. Control RBCs exhibited a small cation-selective whole-cell conductance (236 +/- 38 pS; n = 8) which was highly sensitive to the external Cl(-) concentration: replacement of NaCl in the bath by sodium gluconate induced an increase of this cation conductance by about 85 %. Exposing RBCs to t-butylhydroxyperoxide (1 mM for 10 min) induced a twofold increase in this cation conductance which was further stimulated after replacement of extracellular Cl(-) by gluconate, Br(-), I(-) or SCN(-). In addition, lowering the ionic strength of the bath solution by isosmotic substitution of NaCl by sorbitol activated the cation conductance. The Cl(-)-sensitive and oxidation-induced cation conductance was Ca(2+) permeable, exhibited a permselectivity of Cs(+) > K(+) > Na(+) = Li(+) >> NMDG(+), and was partially inhibited by amiloride (1 mM) and almost completely inhibited by GdCl(3) (150 microM), but was insensitive to TEA, BaCl(2), NPPB, flufenamic acid or quinidine. DIDS (100 microM) reversibly inhibited the activation of the cation conductance by removal of external Cl(-). Oxidation induced haemolysis in NaCl-bathed human RBCs. This haemolysis was attenuated by amiloride (1 mM) and inhibited by replacement of bath Na(+) by the impermeant cation NMDG(+). The Na(+)- and Ca(2+)-permeable conductance might be involved in haemolytic diseases induced by elevated oxidative stress, such as glucose-6-phosphate dehydrogenase deficiency.

Cations↗
PubMed2002

Plasmodium falciparum activates endogenous Cl(-) channels of human erythrocytes by membrane oxidation.

Intraerythrocytic survival of the malaria parasite Plasmodium falciparum requires that host cells supply nutrients and dispose of waste products. This solute transport is accomplished by infection-induced new permeability pathways (NPP) in the erythrocyte membrane. Here, whole-cell patch-clamp and hemolysis experiments were performed to define properties of the NPP. Parasitized but not control erythrocytes constitutively expressed two types of anion conductances, differing in voltage dependence and sensitivity to inhibitors. In addition, infected but not control cells hemolyzed in isosmotic sorbitol solution. Both conductances and hemolysis of infected cells were inhibited by reducing agents. Conversely, oxidation induced identical conductances and hemolysis in non-infected erythrocytes. In conclusion, P.falciparum activates endogenous erythrocyte channels by applying oxidative stress to the host cell membrane.

Animals↗