Ca2+ signalling, voltage-gated Ca2+ channels and praziquantel in flatworm neuromusculature
Greenberg, Robert M.
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Transient changes in calcium (Ca2+) levels regulate a wide variety of cellular processes, and cells employ both intracellular and extracellular sources of Ca2+ for signaling. 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.
Author Posting. © The Author, 2005. This is the author's version of the work. It is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Parasitology 131 (2005): S97-S108, doi:10.1017/S0031182005008346.