Inhibition of voltage-gated sodium channels by bisphenol A in mouse dorsal root ganglion neurons. 2011

Qiang Wang, and Jie Cao, and Qin Zhu, and Chunye Luan, and Xiaodong Chen, and Xiaohua Yi, and Haixia Ding, and Jian Chen, and Jie Cheng, and Hang Xiao
Department of Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010636 Phenols Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D004968 Estrogens, Non-Steroidal Non-steroidal compounds with estrogenic activity. Estrogens, Nonsteroidal,Estrogens, Non Steroidal,Non-Steroidal Estrogens,Nonsteroidal Estrogens
D005727 Ganglia, Spinal Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain. Dorsal Root Ganglia,Spinal Ganglia,Dorsal Root Ganglion,Ganglion, Spinal,Ganglia, Dorsal Root,Ganglion, Dorsal Root,Spinal Ganglion
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001559 Benzhydryl Compounds Compounds which contain the methyl radical substituted with two benzene rings. Permitted are any substituents, but ring fusion to any of the benzene rings is not allowed. Diphenylmethyl Compounds,Compounds, Benzhydryl,Compounds, Diphenylmethyl
D015222 Sodium Channels Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function. Ion Channels, Sodium,Ion Channel, Sodium,Sodium Channel,Sodium Ion Channels,Channel, Sodium,Channel, Sodium Ion,Channels, Sodium,Channels, Sodium Ion,Sodium Ion Channel

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