Sodium Metabisulfite: Effects on Ionic Currents and Excitotoxicity
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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 (I Na) was stimulated, and current inactivation and deactivation were slowed in SMB-treated (30 μM) HL-1 cardiomyocytes. SMB-induced increases of I Na were attenuated in cells treated with ranolazine (10 μM) or eugenol (30 μM). The current-voltage relationship of I Na shifted to slightly more negative potentials in SMB-treated cells, the peak I Na with an EC50 value of 18 μM increased, and the steady-state inactivation curve of I Na shifted to a more positive potential. However, the tail component of the rapidly activating delayed-rectifier K+ current (I Kr) 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 I Na was higher; however, neither the time to peak nor the inactivation time constant (I Na) 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.
KeywordsSodium metabisulfite Voltage-gated Na+ current Delayed-rectifier K+ current Cardiomyocyte Motor neuron Excitotoxicity
We wish to thank Hsien-Chin Huang, Ching-An Kao, Ming-Chun Hsu, Ching-An Kao, and Ming-Chun Hsu for their able assistance with cell preparation.
This work was supported in part by grants from the Taiwan National Science Council (NSC-101-2320-B-006-009 and NSC-102-2314-B-006-051-MY3), Ministry of Science and Technology, ROC, (105-2314-B-006-013, 106-2314-B-006-034- and 106-2320-B-006-055-), the Aim for the Top University Project, National Cheng Kung University, and Chi-Mei Medical Center (CMNCKU10515).
Compliance with Ethical Standards
All experiments including the procedures for animal experimentation were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at the National Cheng Kung University.
Conflict of Interest
The authors declare that they have no conflicts of interest.
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