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双酚 A 调节大鼠背根神经节神经元钙电流和细胞内钙浓度。

Bisphenol A modulates calcium currents and intracellular calcium concentration in rat dorsal root ganglion neurons.

机构信息

School of Public Health, Guiyang Medical University, 9 Beijing Road, Guiyang 550004, China.

出版信息

J Membr Biol. 2013 May;246(5):391-7. doi: 10.1007/s00232-013-9545-8. Epub 2013 Apr 11.

Abstract

The endocrine-disrupting chemical bisphenol A (BPA) is used to manufacture plastics including food containers, and it may leach into these containers. Consumption of BPA that has leached out of plastics may be harmful as recent research highlighted that BPA can induce alterations in the nervous system. In the present work, we studied the effects of BPA on Ca²⁺ channels in dorsal root ganglion (DRG) neurons. Using whole-cell patch-clamp recordings, we found that I(Ca) could be reduced by BPA in a concentration-dependent manner. Additionally, BPA shifted the activation curve of calcium currents toward a depolarizing direction and increased the slope factor of the curve. The inactivation curve for the currents was also assessed, and the curve shifted toward the depolarizing direction, although it was not significant. Moreover, inhibitory effects of BPA on the increments of intracellular Ca²⁺ concentrations (Ca²⁺) induced by 50 mM KCl were observed in DRG neurons using a laser scanning confocal microscopy assay. Further work revealed that the PKA and PKC pathways may be involved in the inhibitory effects of BPA since the PKA antagonist GÖ-6983 and the PKC antagonist H-89 significantly alleviated the inhibitory effects of BPA on I(Ca). As such, the results of the present study provide direct evidence that BPA decreases I(Ca) and impairs calcium homeostasis, which may be involved in any toxic effects of BPA on DRG neurons.

摘要

环境内分泌干扰物双酚 A(BPA)用于制造包括食品容器在内的塑料,它可能会渗出这些容器。最近的研究强调,BPA 可诱导神经系统发生改变,因此从塑料中渗出的 BPA 的消耗可能是有害的。在本工作中,我们研究了 BPA 对背根神经节(DRG)神经元钙通道的影响。通过全细胞膜片钳记录,我们发现 BPA 可浓度依赖性地减少 I(Ca)。此外,BPA 将钙电流的激活曲线向去极化方向移动,并增加曲线的斜率因子。还评估了电流的失活曲线,尽管没有统计学意义,但曲线也向去极化方向移动。此外,使用激光扫描共聚焦显微镜检测发现,BPA 对 50 mM KCl 诱导的 DRG 神经元内 Ca²⁺浓度增加具有抑制作用。进一步的研究表明,PKA 和 PKC 途径可能参与了 BPA 的抑制作用,因为 PKA 拮抗剂 GÖ-6983 和 PKC 拮抗剂 H-89 显著减轻了 BPA 对 I(Ca)的抑制作用。因此,本研究的结果提供了直接证据,表明 BPA 可减少 I(Ca)并破坏钙稳态,这可能与 BPA 对 DRG 神经元的任何毒性作用有关。

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