Parasite neuromusculature and its utility as a drug target

Ca2+ signalling, voltage-gated Ca2+ channels and praziquantel in flatworm neuromusculature

a1 Marine Biological Laboratory, 7 MBL Street, Woods Hole, MA 02543 USA.

Article author query
greenberg rm   [PubMed][Google Scholar] 


Transient changes in calcium (Ca2+) levels regulate a wide variety of cellular processes, and cells employ both intracellular and extracellular sources of Ca2+ for signalling. Praziquantel, the drug of choice against schistosomiasis, disrupts Ca2+ homeostasis in adult worms. This review will focus on voltage-gated Ca2+ channels, which regulate levels of intracellular Ca2+ by coupling membrane depolarization to entry of extracellular Ca2+. Ca2+ channels are members of the ion channel superfamily and represent essential components of neurons, muscles and other excitable cells. Ca2+ channels are membrane protein complexes in which the pore-forming α1 subunit is modulated by auxiliary subunits such as β and α2δ. Schistosomes express two Ca2+ channel β subunit subtypes: a conventional subtype similar to β subunits found in other vertebrates and invertebrates and a novel variant subtype with unusual structural and functional properties. The variant schistosome β subunit confers praziquantel sensitivity to an otherwise praziquantel-insensitive mammalian Ca2+ channel, implicating it as a mediator of praziquantel action.

Key Words: Praziquantel; schistosome; calcium; calcium channels.

c1 Marine Biological Laboratory, 7 MBL Street, Woods Hole MA 02543. Tel: (508) 289-7910. Fax: (508) 540-6902. E-mail: