From Plastic-Bottle-Toxin to Sodium Channel Blocker: A New Role for Bisphenol A

Abstract

Bisphenol A has reached public attention due to its presence in food and beverages following leaching from plastic containers.. It is a monomer that is polymerized to manufacture polycarbonate plastic food wrappings and it is detectable in the blood of human populations in developed countries (Palanza et al. 2008, Environmental Research). In animal studies and in vitro bisphenol A was shown to have estrogenic effects. Data link bisphenol A exposure to a variety of diseases including miscarriage, menstrual pain and cardiovascular syndromes.The human heart voltage-gated sodium channel hNav1.5 was expressed in HEK293t cells to determine the effect of bisphenol A on sodium channel function.With whole-cell patch clamp analysis, we show that bisphenol A reduces the peak sodium current through hNav1.5 from a holding potential of −120 mV with an EC50 of 54 ± 8 µM This concentration is considerably higher than has been found in beverages from plastic bottles. However, compared to other known sodium channel blockers, such as lamotrigine or lidocaine, its efficacy is approximately ten-fold higher.Bisphenol A shifts steady-state fast inactivation to more hyperpolarized potentials, whereas voltage-dependence of activation is unaffected. As with local anesthetics, bisphenol A binds preferentially to the inactivated state. The association time constant, as determined by a single exponential fit of peak current decline induced by 30 µM bisphenol A is approximately 14 times faster than that induced by 300 µM lidocaine.In conclusion, we have determined that bisphenol A has blocking effects on hNav1.5 sodium currents that are more pronounced than those of known blockers, such as lidocaine or lamotrigine.Funding: AOR and BAW: BBSRC. AL: Robert-Bosch-Foundation.