重组人红细胞生成素对大鼠背根神经节细胞钙通道的调节作用

Modulatory effects of recombinant human erythropoietin on calcium channels in rat dorsal root ganglion neurons

目的观察重组人红细胞生成素(rhEpo)对大鼠背根神经节(DRG)细胞上钙通道的调节作用,从离子通道和电生理的角度探讨rhEpo对脊髓神经细胞的保护机制。方法采用全细胞膜片钳技术,记录急性分离的大鼠背根神经节细胞上钙电流。结果重组人红细胞生成素呈剂量依赖性(5～25 U/ml)增大背根神经节细胞上的电压依赖性钙电流,对峰电流最大增幅可达(46.0±4.6)%,可以被特异性钙通道阻断剂硝苯地平(Nifedipine)、氟桂利嗪(Fiunarizine)部分阻断,而被非特异性钙通道阻断剂氯化锂(NiCl_2)几乎完全阻断。结论重组人红细胞生成素调节背根神经节细胞上的电压依赖性的T型和L型钙通道,从而增加细胞内钙的浓度,本实验提示重组人红细胞生成素可能通过调节脊髓神经细胞上的电压依赖性钙通道来引起后续的一系列生物效应从而达到保护脊髓神经细胞的作用。

Objective To investigate the modulatory effects of recombinant human erythropoietin （rhEpo） on calcium channels of rat dorsal root ganglion （DRG） neurons in order to explore the neuroprotective mechanism and provide evidence for the treatment of spinal cord injury （SCI）. Methods Wholecell patch clamp technique was used to determine calcium current on acutely dissociated DRG neurons. Results rhEpo at 5-25 U/ml dose-dependently increased voltage-dependent calcium current of DRG neurons and the amplitude of peak current was increased by （46.0 ± 4.6） %, which was partly blocked by the specific blockers of calcium channel, such as Nifedipine, Flunarizine, but almost completely blocked by NiCl2 ,-one of the nonspecific blockers of calcium channel. Conclusion rhEpo regulates rat DRG neuron＇s T and L type calcium currents and increases intracellular free Ca^2＋（ [ Ca^2＋ ] i）. It is suggested that one of the mechanisms by which rhEpo acts on the injured spinal cord neurons is by modulation of the voltagedependent calcium channels on the neurons.