Plasmodia (P) maintain a high Ca2+ environment (green) when invading a red blood cell (E).

Life without Ca2+—a vital enzyme cofactor and essential second messenger—is no life at all. Consider then the challenge faced by Plasmodia, the causal agent of malaria. These parasites spend most of their life inside red blood cells, whose cytoplasmic levels of Ca2+ are far too low to support their survival. On page 103, Gazarini et al. now show that Plasmodia get around this problem by maintaining a high Ca2+ level within the parasitophorous vacuole (PV), their home in the red blood cell.

Previous studies suggested that the PV membrane (PVM) was something of a sieve, and that the ionic environment inside it should be similar to the host cytoplasm. The researchers tested this by using indicator dyes to measure Ca2+ levels in the cytosol and inside the PVM. They found that Plasmodia maintain local Ca2+ levels that are 100–1,000 times higher than those in the red blood cell cytoplasm—easily enough to supply their internal stores. Those stores are essential for regulation of parasite activity, including a Ca2+-based signaling system that responds to the host hormone melatonin. Ca2+ is also required for parasite maturation, as even a temporary two hour decrease in PV Ca2+ concentration strongly decreased the number of Plasmodia that developed to the infectious stage.

It is not yet clear how Ca2+ levels are kept so high in the PVM. The orientation of the host plasma membrane is inverted to form the PVM during parasite invagination, so inverted Ca2+-ATPase pumps from the host membrane may be able to pump Ca2+ into the PVM. A drug that interferes with this PVM Ca2+ accumulation without affecting the red blood cells themselves might be a valuable tool in our arsenal against this devastating parasite. ▪