Ca2+ signalling, voltage-gated Ca2+ channels and praziquantel in flatworm neuromusculature.
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 alpha1 subunit is modulated by auxiliary subunits such as beta and alpha2delta. Schistosomes express two Ca2+ channel beta subunit subtypes: a conventional subtype similar to beta subunits found in other vertebrates and invertebrates and a novel variant subtype with unusual structural and functional properties. The variant schistosome beta subunit confers praziquantel sensitivity to an otherwise praziquantel-insensitive mammalian Ca2+ channel, implicating it as a mediator of praziquantel action.
Marine Biological Laboratory, 7 MBL Street, Woods Hole, MA 02543, USA. rgreenberg@mbl.edu
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D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010986:Platyhelminths / Q000187:drug effects / Q000502:physiology; D011223:Praziquantel / Q000737:chemistry / Q000494:pharmacology*; D012547:Schistosoma / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
D000871:Anthelmintics; D015220:Calcium Channels; D011223:Praziquantel