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.
Background
Voltage-gated calcium (Ca v ) channels couple membrane depolarisation to the entry of Ca 2+ that, in turn, is funda-mental in a variety of cellular events such as contraction [1,2], changes in gene expression [3] and neurotransmitter release [4,5]. Ca v channels belong to the super-family