Calcium channels of schistosomes: unresolved questions and unexpected answers

Parasitic flatworms of the genus Schistosoma are the causative agents of schistosomiasis, a highly prevalent, neglected tropical disease that causes significant morbidity in hundreds of millions of people worldwide. The current treatment of choice against schistosomiasis is praziquantel (PZQ), which is known to affect Ca(2+) homeostasis in schistosomes, but which has an undefined molecular target and mode of action. PZQ is the only available antischistosomal drug in most parts of the world, making reports of PZQ resistance particularly troubling. Voltage-gated Ca(2+) (Ca(v)) channels have been proposed as possible targets for PZQ, and, given their central role in the neuromuscular system, may also serve as targets for new anthelmintic therapeutics. Indeed, ion channels constitute the majority of targets for current anthelmintics. Ca(v) channel subunits from schistosomes and other platyhelminths have several unique properties that make them attractive as potential drug targets, and that could also provide insights into structure-function relationships in, and evolution of, Ca(v) channels.