calcimycin and Malaria

1. The effects of Ca2+ and the calcium ionophore A23187 on the intraerythrocytic development of the asexual forms of Plasmodium yoelii were examined. 2. Erythrocyte-free parasites obtained by saponin lysis of infected cells remained viable after exposure to 1 mM Ca2+. 3. A23187 inhibited the growth of P. yoelii and the inhibition was augmented by Ca2+ in cells infected with parasites at young stage of development. 4. A23187-treated infected cells disappeared from the circulation shortly after intravenous injection and this disappearance was profound in infected cells treated with the ionophore in the presence of Ca2+.

Topics: Animals; Calcimycin; Calcium; Erythrocytes; Female; Malaria; Mice; Mice, Inbred ICR; Plasmodium yoelii

The Ca2+ ionophore A23187 has much less capacity to induce Ca2+ uptake of red cells from P. berghei-infected mice than of cells from normal mice. The reduction in Ca2+ uptake occurs in both uninfected and infected cells at all stages in the infected blood, as shown from experiments with cells separated on colloidal silica density gradient. Measurement of the ionophore concentration in the medium reveals that the ionophore is partitioned into red cells from infected blood to a greater extent than cells from normal blood. The reduction in A23187-induced Ca2+ uptake may be due to difference in the interaction of red cell membrane with the ionophore, and its already high Ca2+ permeability.

Topics: Animals; Anti-Bacterial Agents; Biological Transport; Calcimycin; Calcium; Erythrocytes; Malaria; Mice; Plasmodium berghei

The calcium content and transport processes of Plasmodium chabaudi-infected rat erythrocytes were analyzed by atomic absorption spectroscopy and 45Ca2+ flux measurements. Infected erythrocytes, after fractionation on metrizamide gradients according to stage of parasite development, exhibited progressively increasing levels of Ca2+ with schizont and gametocytes containing 10- to 20-fold greater calcium levels than normal cells (0.54 +/- 0.25 nmol/10(8) cells). 45Ca2+ flux experiments showed both increased influx and decreased efflux in infected erythrocytes. Tris/NH4Cl lysis of normal erythrocytes preloaded with 45Ca2+ with the Ca2+ ionophore A23187 released less than 90% of cell calcium after incubation in ethyleneglycol bis(aminoethylether) N,N'-tetraacetic acid containing buffer, whereas lysis of the infected erythrocyte membrane resulted in release of 10-20% cell Ca2+, with the remaining portion associated with the isolated parasite fraction. This information together with the effects of various metabolic inhibitors indicates the presence of a parasite Ca2+ compartment in P. chabaudi-infected erythrocytes. Dicyclohexylcarbodiimide (DCCD) an inhibitor of proton ATPases of chloroplasts, bacteria, yeast, and mitochondria, and the proton ionophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP), inhibited Ca2+ influx and stimulated efflux from infected cells. These results combined with evidence for a DCCD- and CCCP-sensitive membrane potential in P. chabaudi-infected cells (Mikkelsen et al., accompanying manuscript) suggest that Ca2+ transport of intraerythrocytic parasites is coupled to a proton-motive force across the Plasmodia plasma membrane.

Topics: Animals; Calcimycin; Calcium; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Dicyclohexylcarbodiimide; Edetic Acid; Erythrocyte Membrane; Erythrocytes; Hydrogen; Ion Channels; Malaria; Male; Plasmodium; Rats