Predicted changes in the Vm of P falciparum–infected RBCs during the asexual reproduction cycle of the parasite and changes in selected homeostatic variables after suspension of 35-hour postinvasion infected RBCs in either high or low ionic-strength media. (A) Predicted changes in the Vm during the asexual reproduction cycle of the parasite. Predicted changes in (B) the Vm, (C) the relative cell volume, and (D) the pHi after suspension of 35-hour postinvasion infected RBCs in iso-osmotic NaCl (dot/dash lines), sucrose (solid lines), and sorbitol (dashed lines) solutions at RT. The experimental protocol used to obtain the data shown in panels B, C, and D was as follows: 35-hour postinvasion infected RBCs were washed into iso-osmotic NaCl solution (pH 7.4) at RT and left for 30 minutes, then the infected RBCs were resuspended for 8.5 minutes in each of the different iso-osmotic solutions at RT. The 8.5-minute time scale depicts the average lysis time for infected RBCs suspended in iso-osmotic sorbitol solution at RT (see Table 2) and was set by adjusting the maximum sorbitol permeability in the model to 2.7 hour–1 (the default values for all other variables were unchanged). Note that the actual NPPB-sensitive rate constant (derived from the sorbitol uptake data measured in iso-osmotic NaCl solution presented in Figure 2A) was 15 ± 3 hour–1 (n = 3) and was not used in the modeling because this resulted in faster than expected lysis rates. A 5-mM external Cl– concentration was used when predicting the effect of low ionic-strength solutions. In panel C, all volumes are expressed relative to the RBC volume at the time of invasion, defined as 1, and the horizontal top line indicates the mean critical hemolytic relative cell volume.
