Creation by mutagenesis of a mammalian Ca(2+) channel beta subunit that confers praziquantel sensitivity to a mammalian Ca(2+) channel.

Voltage-gated Ca(2+) channel beta subunits are important modulators of the pore-forming alpha(1) subunit. We have cloned two schistosome beta subunits that confer sensitivity to the antischistosomal drug praziquantel (PZQ) to an otherwise insensitive mammalian alpha(1) subunit. The primary site of beta subunit interaction with alpha(1) subunits is the beta interaction domain (BID). The BID contains two conserved serines (225, 235 in rat beta2a) that constitute consensus sites for protein kinase C phosphorylation. However, these serines are absent in these schistosome beta subunits. Here we show that the capability to confer PZQ sensitivity can be created in the rat beta2a subunit by eliminating both serines in the BID. These results are consistent with, and should help our understanding of, the selective toxicity of PZQ.