Subcellular pH and Ca2+ in Plasmodium falciparum: implications for understanding drug resistance mechanisms.

摘要

Live cell imaging plays an ever increasing role in the investigation of the human malaria parasite Plasmodium falciparum. For example, fluorescence microscopy and fluorescence spectroscopy, in combination with ion specific fluorochromes, have been used to determine steady-state and dynamic pH and Ca2+ concentrations within different compartments of the infected erythrocyte, including the parasite's digestive vacuole that is thought to be the target of several important antimalarial drugs. The data obtained, using live cell imaging, have led to the hypothesis that the digestive vacuole serves as a dynamic intracellular Ca2+ store or that changes in the pH gradient across the digestive vacuolar membrane are associated with certain drug resistance phenotypes. However, both these hypotheses and the underpinning data have been challenged on the grounds that alternative explanations are possible to account for the data obtained. Here we review the known problems that can arise when imaging live P. falciparum-infected erythrocytes.