Atypical properties of a conventional calcium channel β subunit from the platyhelminth Schistosoma mansoni

BACKGROUND: The function of voltage-gated calcium (Ca(v)) channels greatly depends on coupling to cytoplasmic accessory β subunits, which not only promote surface expression, but also modulate gating and kinetic properties of the α(1 )subunit. Schistosomes, parasitic platyhelminths that cause schistosomiasis, express two β subunit subtypes: a structurally conventional β subunit and a variant β subunit with unusual functional properties. We have previously characterized the functional properties of the variant Ca(v)β subunit. Here, we focus on the modulatory phenotype of the conventional Ca(v)β subunit (SmCa(v)β) using the human Ca(v)2.3 channel as the substrate for SmCa(v)β and the whole-cell patch-clamp technique. RESULTS: The conventional Schistosoma mansoni Ca(v)β subunit markedly increases Ca(v)2.3 currents, slows macroscopic inactivation and shifts steady state inactivation in the hyperpolarizing direction. However, currents produced by Ca(v)2.3 in the presence of SmCa(v)β run-down to approximately 75% of their initial amplitudes within two minutes of establishing the whole-cell configuration. This suppressive effect was independent of Ca(2+), but dependent on intracellular Mg(2+)-ATP. Additional experiments revealed that SmCa(v)β lends the Ca(v)2.3/SmCa(v)β complex sensitivity to Na(+ )ions. A mutant version of the Ca(v)β subunit lacking the first forty-six amino acids, including a string of twenty-two acidic residues, no longer conferred sensitivity to intracellular Mg(2+)-ATP and Na(+ )ions, while continuing to show wild type modulation of current amplitude and inactivation of Ca(v)2.3. CONCLUSION: The data presented in this article provide insights into novel mechanisms employed by platyhelminth Ca(v)β subunits to modulate voltage-gated Ca(2+ )currents that indicate interactions between the Ca(2+ )channel complex and chelated forms of ATP as well as Na(+ )ions. These results have potentially important implications for understanding previously unknown mechanisms by which platyhelminths and perhaps other organisms modulate Ca(2+ )currents in excitable cells.