托吡酯对酸敏感离子通道1a调控作用的研究

The regulatory effect of topiramate on acid-sensing ion channel 1a

目的探讨抗癫痫药物托吡酯(topiramate,TPM)对酸敏感离子通道1a(acid-sensing ion channel 1a,ASIC1a)的调控作用。方法 CHO细胞转染酸敏感离子通道(acid-sensing ion channels,ASICs)不同亚型后,通过全细胞记录膜片钳技术研究TPM对ASICs各亚型调节作用,以及对ASIC1a的具体调节模式;通过Western blot定量分析TPM对ASIC1a蛋白表达的影响。结果 TPM仅对ASIC1a同聚体通道产生的内向电流具有增强效应;这种增强效应具有剂量依赖性,且与胞外p H值相关;TPM必须与酸共给的情况下才能对ASIC1a发挥增强效应;并且TMP不影响ASIC1a的蛋白表达。结论 TPM对ASIC1a同聚体通道产生的内向电流具有直接增强作用,这可能是其治疗癫痫发作的作用机制之一。

Objective To explore the regulatory effect of topiramate（ TPM） on acid-sensing ion channel 1 a（ ASIC1 a）. Methods Different subunits of acid-sensing ion channels（ ASICs） were expressed on the CHO cell line,and then the specific model regulation of TPM on the different subunits of ASICs was studied by the whole cell patch-clamp recording technique,especially on homopolymer channel of ASIC1 a. The effect of TPM on the expression of ASIC1 a protein was studied by Western blot. Results TPM enhanced the inward current generated by homopolymer channel of ASIC1 a,while had no effect on all the other units. The enhancement was dose-dependent and associated with extracellular PH value only just with the presence of acid. TPM did not affect the protein expression of ASIC1 a. Conclusion TPM has a direct enhancement on the inward current generated by the homopolymer channel of ASIC1 a,hinting that ASIC1 a may be involved in the anti-epileptic mechanisms of TPM.