Bisphenol A inhibits voltage-activated Ca(2+) channels in vitro: mechanisms and structural requirements.
Level 5 - mechanism / opinion, no new human data
In vitro bench study on cultured rodent cells and recombinant human channels
PubMed 23197648 · doi:10.1124/mol.112.081372
What was done
The authors evaluated the direct effects of Bisphenol A (BPA) and related phenolic compounds on voltage-activated Ca2+ channels. They recorded macroscopic Ba2+ and Ca2+ currents in native rodent cells (L-, N-, P/Q-, and T-type channels in rat pituitary GH3 cells, mouse dorsal root ganglion neurons, and mouse cardiac myocytes) and recombinant human R-type channels expressed in HEK293 cells. Biophysical, pharmacological, and structure-activity analyses were performed to identify the binding mechanism and essential structural features.
What was found
BPA rapidly and reversibly blocked all tested native and recombinant Ca2+ channels with similar potencies, yielding EC50 values between 26 and 35 μM. On recombinant human R-type channels, inhibition occurred without requiring intracellular signaling, was not voltage- or use-dependent, and did not modify channel gating kinetics, indicating direct resting-state binding to an external site outside the pore. Structure-activity analysis demonstrated that optimal block required an angulated orientation of the two aromatic rings linked by an sp3-hybridized carbon that is double-alkylated or double-trifluoromethylated.
Why it matters
This study identifies voltage-gated Ca2+ channels as a direct non-genomic target of BPA, providing structural and biophysical mechanisms for xenobiotic-induced disruption of excitable cells.
Limits
The study was entirely in vitro, and the effective concentrations (EC50 of 26–35 μM) are substantially higher than typical human environmental serum exposures. The abstract does not report sample sizes (number of cells or independent recording runs) or in vivo functional outcomes.
Cited by
- supports Acute exposure to BPA inhibits voltage-gated calcium channels in cardiomyocytes, impairing calcium handling and heart contractions.