Sodium Metabisulfite: Effects on Ionic Currents and Excitotoxicity

Ming Chi Lai, Te Yu Hung, Kao Min Lin, Pi Shan Sung, Shyh Jong Wu, Chih Sheng Yang, Yi Jen Wu, Jing Jane Tsai, Sheng Nan Wu, Chin Wei Huang

研究成果: Article同行評審

12 引文 斯高帕斯(Scopus)

摘要

How sodium metabisulfite (SMB; Na2S2O5), a popular food preservative and antioxidant, interacts with excitable membrane and induces excitotoxicity is incompletely understood. In this study, the patch-clamp technique was used to investigate and record the electrophysiological effect of SMB on electrically excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western blotting, to analyze sodium channel expression on hippocampi after chronic SMB treatment. It was found that voltage-gated Na+ current (INa) was stimulated, and current inactivation and deactivation were slowed in SMB-treated (30 μM) HL-1 cardiomyocytes. SMB-induced increases of INa were attenuated in cells treated with ranolazine (10 μM) or eugenol (30 μM). The current-voltage relationship of INa shifted to slightly more negative potentials in SMB-treated cells, the peak INa with an EC50 value of 18 μM increased, and the steady-state inactivation curve of INa shifted to a more positive potential. However, the tail component of the rapidly activating delayed-rectifier K+ current (IKr) was dose-dependently inhibited. Cell-attached voltage-clamp recordings in SMB-treated cells showed that the frequency of action currents and prolonged action potential were higher. In SMB-treated NSC-34 neurons, the peak INa was higher; however, neither the time to peak nor the inactivation time constant (INa) changed. Pilocarpine-induced seizures were exacerbated, and acute neuronal damage and chronic mossy fiber sprouting increased in SMB-treated rats. Western blotting showed higher expression of the sodium channel in cells after chronic SMB treatment. We conclude that SMB contributes to the sodium channel-activating mechanism through which it alters cellular excitability and excitotoxicity in wide-spectrum excitable cells.

原文English
頁(從 - 到)1-15
頁數15
期刊Neurotoxicity research
34
發行號1
DOIs
出版狀態Published - 2018 7月 1

All Science Journal Classification (ASJC) codes

  • 神經科學 (全部)
  • 毒理學

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