Session: MON 338-354-Physiological Impacts of Endocrine Disrupting Chemicals
Poster Board MON-353
The inverted-U shaped response was maintained in the presence of the ERalpha-selective blocker MPP, suggesting that the opposing actions of ERbeta (stimulatory) and ERalpha (inhibitory) do not play a major role in defining the observed concentration response characteristics. The rapid cardiac action of BPA is mediated by alterations of Ca handling, including increases in sarcoplasmic reticulum (SR) Ca reuptake and release (Yan et al, 2011). Interestingly, the effects of BPA on these individual elements of myocyte Ca handling were monotonic rather than nonmonotonic. Over the concentration range of 10-12 to 10-6 M, BPA progressively increased Ca spark frequency (an indication of SR spontaneous Ca release) and Ca transient decline rate (an indication of SR Ca reuptake rate). BPA also progressively inhibited the L-type Ca current with monotonic dose-response characteristics. At microM concentrations, such inhibition of the L-type Ca current reduces Ca influx and likely suppresses myocyte contraction and contributes to the inhibitory phase of the inverted U-shaped dose response curves. The combined and opposing effects of progressively increased SR Ca reuptake/release and decreased Ca influx likely produce the inverted-U shaped dose responses of estrogens.
In conclusion, our results suggest that the nonmonotonic dose response of BPA in the heart is the sum of multiple monotonic effects on individual Ca handling elements.
Nothing to Disclose: QL, XG, YC, HSW
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