Bisphenol A differently inhibits CaV3.1, Ca V3.2 and Ca V3.3 calcium channels.

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.