Abstract
Bisphenol A (BPA) is an estrogenic endocrine disruptor associated with a variety of pathologies that have raised public health concerns. Epidemiological studies show a relationship between urinary BPA levels and cardiovascular diseases, but the molecular actions of BPA on the cardiovascular system remain largely unknown. Estrogen regulates the expression of large conductance voltage/Ca2+‐activated K+ (BK) channels; however, effects of BPA on BK channel expression are unknown. We tested the hypothesis that BPA regulates BK channel expression though genomic mechanisms involving nuclear estrogen receptors (ER). Rat aortae were harvested and placed in tissue culture for 48–72 hour treatment with BPA. BK channel expression was determined by RT‐PCR, Western blot, and whole‐cell patch clamp. BPA decreased the expression of BK α subunit mRNA and protein. Penitrem A‐sensitive BK current was reduced in cells from BPA‐treated aortae. The effect of BPA to reduce BK channel mRNA, protein, and current was blocked by ICI 182,780, an ER antagonist. These data suggest that BPA decreases BK channel expression via nuclear ER and may represent one mechanism by which BPA exposure is linked to cardiovascular disease. Supported by T‐32 HL‐090610.
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