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J. Biol. Chem., Vol. 276, Issue 40, 36873-36876, October 5, 2001

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ACCELERATED PUBLICATION
Schistosome Calcium Channel  Subunits
UNUSUAL MODULATORY EFFECTS AND POTENTIAL ROLE IN THE ACTION OF THE ANTISCHISTOSOMAL DRUG PRAZIQUANTEL^*

Andrea B. Kohn, Peter A. V. Anderson^§¶, Jessica M. Roberts-Misterly, and Robert M. Greenberg^§

From the  Whitney Laboratory and the Departments of ^§ Neuroscience and ^¶ Physiology, University of Florida, St. Augustine, Florida 32080

Schistosomes are parasitic flatworms that cause schistosomiasis, a major tropical disease. The current drug of choice against schistosomiasis is praziquantel (PZQ), which has minimal side effects and is potent against all schistosome species. The mode of action of PZQ is unknown, though the drug clearly affects Ca²⁺ homeostasis in worms, and there is indirect evidence for interaction of PZQ with schistosome voltage-gated Ca²⁺ channels. We have cloned and expressed two Ca²⁺ channel  subunits, one from Schistosoma mansoni and one from Schistosoma japonicum. These two subunits (SmCa_vA and SjCa_v) have structural motifs that differ from those found in other known  subunits. Surprisingly, coexpression of either SmCa_vA or SjCa_v with a cnidarian (CyCa_v1) or mammalian (Ca_v2.3) Ca²⁺ channel ₁ subunit results in a striking reduction in current amplitude. In the case of Ca_v2.3, this current reduction can be partially reversed by addition of 100 nM PZQ, which results in a significant increase in current amplitude. Thus, these unusual schistosome  subunits can confer PZQ sensitivity to an otherwise PZQ-insensitive mammalian Ca²⁺ channel, indicating that a possible target for PZQ action is the interaction between  subunits and pore-forming ₁ subunits in schistosomes.

These nucleotide and amino acid sequence can be accessed through NCBI Nucleotide Database under NCBI accession numbers AY033597 for SjCa_v and AY033598 for SmCa_vA.

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