Research article

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

Vicenta Salvador-Recatalà^1,3 , Toni Schneider² and Robert M Greenberg^1,3

¹Marine Biological Laboratory 7 MBL Street Woods, Hole, MA 02543, USA

²Institute for Neurophysiology & Center for Molecular Medicine Cologne (CMMC) Robert-Koch-Str. 39 D-50931 Köln, Germany

³Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA

author email corresponding author email

BMC Physiology 2008, 8:6doi:10.1186/1472-6793-8-6

Published:	26 March 2008

Abstract

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 α₁ 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_vβ subunit. Here, we focus on the modulatory phenotype of the conventional Ca_vβ subunit (SmCa_vβ) using the human Ca_v2.3 channel as the substrate for SmCa_vβ and the whole-cell patch-clamp technique.

Results

The conventional Schistosoma mansoni Ca_vβ subunit markedly increases Ca_v2.3 currents, slows macroscopic inactivation and shifts steady state inactivation in the hyperpolarizing direction. However, currents produced by Ca_v2.3 in the presence of SmCa_vβ run-down to approximately 75% of their initial amplitudes within two minutes of establishing the whole-cell configuration. This suppressive effect was independent of Ca²⁺, but dependent on intracellular Mg²⁺-ATP. Additional experiments revealed that SmCa_vβ lends the Ca_v2.3/SmCa_vβ complex sensitivity to Na⁺ ions. A mutant version of the Ca_vβ subunit lacking the first forty-six amino acids, including a string of twenty-two acidic residues, no longer conferred sensitivity to intracellular Mg²⁺-ATP and Na⁺ ions, while continuing to show wild type modulation of current amplitude and inactivation of Ca_v2.3.

Conclusion

The data presented in this article provide insights into novel mechanisms employed by platyhelminth Ca_vβ subunits to modulate voltage-gated Ca²⁺ currents that indicate interactions between the Ca²⁺ 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 Ca²⁺ currents in excitable cells.