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Bisphenol A differently inhibits CaV3.1, CaV3.2 and CaV3.3 calcium channels

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Abstract

Bisphenol A (BPA) is a widespread environmental contaminant detected in urine of 93 % of investigated US population. Recent epidemiological studies found correlation between BPA exposure and diseases including cardiovascular and neuronal disorders. BPA targets include hormone receptors and voltage-dependent ion channels. T-type calcium channels are important regulatory elements in both cardiovascular and neuronal system. Therefore, we investigated effects of BPA on T-type calcium channels. Calcium current flowing through recombinant T-type calcium channels expressed in HEK 293 cells was measured using whole-cell patch clamp. BPA inhibited the current through individual T-type calcium channel subtypes in a concentration-dependent manner with two distinguishable components in these concentration-dependencies. Nanomolar concentrations of BPA inhibited calcium current through T-type calcium channels in the order of efficiency CaV3.2 ≥ CaV3.1 > CaV3.3 without affecting voltage dependence and kinetics of channel gating. Micromolar concentrations of BPA accelerated kinetics of current decay, shifted voltage dependence of steady-state inactivation towards more negative values and inhibited current amplitudes. We suggest that BPA acts as a modifier of channel gating and directly plugs conductive channel pore at high concentration. Concentration range in which inhibition was observed corresponds to concentrations detected in human fluids and therefore may be relevant for evaluation of health effects of BPA.

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Acknowledgments

This work was supported by the grant VEGA 2/0044/13. Authors wish to thank Emília Kocúrová for an excellent technical assistance and to Dominika Valachová, Juraj Fuska and Helena Jánošíková for help with certain experiments.

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Authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34, Bratislava, Slovak Republic

    Pavlovičová Michaela, Karmažínová Mária, Huláková Silvia & Lacinová Ľubica

  2. Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32, Bratislava, Slovakia

    Huláková Silvia

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  1. Pavlovičová Michaela
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  2. Karmažínová Mária
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  3. Huláková Silvia
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Correspondence to Lacinová Ľubica.

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Michaela, P., Mária, K., Silvia, H. et al. Bisphenol A differently inhibits CaV3.1, CaV3.2 and CaV3.3 calcium channels. Naunyn-Schmiedeberg's Arch Pharmacol 387, 153–163 (2014). https://doi.org/10.1007/s00210-013-0932-6

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  • DOI: https://doi.org/10.1007/s00210-013-0932-6

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