Inhibition of voltage-gated sodium channels by bisphenol A in mouse dorsal root ganglion neurons.
Bisphenol A (BPA), an estrogenic compound, is contained in cans, polycarbonate bottles, and some dental sealants. Exposure to BPA might have potential toxicological effects on the nervous system. Previous studies have demonstrated that BPA may affect ion channel function, but the effects of BPA on voltage-gated sodium channels are unknown. Herein, we report the effects of BPA on TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ currents, using a conventional whole-cell patch clamp technique from acutely isolated mouse dorsal root ganglion neurons. BPA inhibited TTX-S Na+ currents and TTX-R Na+ currents, the effects of BPA were rapid, reversible and in a concentration-dependent manner. Moreover, BPA could shift the voltage-gated activation curve for TTX-S Na+ channel in the hyperpolarizing direction without changing that for TTX-R Na+ channel; shift the steady-state inactivation curve for TTX-S Na+ channel in the depolarizing direction without changing that for TTX-R Na+ channel; and lengthen the time course of recovery from inactivation for both TTX-S Na+ current and TTX-R Na+ current. We also found that PKC inhibitor GÖ-6983 and PKA inhibitor H-89 blocked the BPA-induced inhibition of Na+ currents. Considering its complex modulatory effects on voltage-gated sodium channels, BPA might have potential toxicological effects on the nervous system and lead to a change in excitability of nociceptive afferent fibers.
Department of Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Qiang
Q
Wang
Jie
J
Cao
Qin
Q
Zhu
Chunye
C
Luan
Xiaodong
X
Chen
Xiaohua
X
Yi
Haixia
H
Ding
Jian
J
Chen
Jie
J
Cheng
Hang
H
Xiao
D000818:Animals; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000633:toxicity*; D015222:Sodium Channels / Q000378:metabolism*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D015222:Sodium Channels; C006780:bisphenol A; D000098826:Bisphenol A Compounds