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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalNeurotoxicity Research
Volume34
Issue number1
DOIs
Publication statusPublished - 2018 Jul 1

Fingerprint

Sodium Channels
Pilocarpine
Clamping devices
Neurons
Rats
Electric potential
Cells
Food Preservatives
Eugenol
Cardiac Myocytes
Seizures
Antioxidants
Western Blotting
Membranes
Fibers
Patch-Clamp Techniques
Action Potentials
sodium metabisulfite
Tail
Hippocampus

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Toxicology

Cite this

Lai, Ming Chi ; Hung, Te Yu ; Lin, Kao Min ; Sung, Pi-Shan ; Wu, Shyh Jong ; Yang, Chih Sheng ; Wu, Yi-Jen ; Tsai, Jing Jane ; Wu, Sheng-Nan ; Huang, Chin-Wei. / Sodium Metabisulfite : Effects on Ionic Currents and Excitotoxicity. In: Neurotoxicity Research. 2018 ; Vol. 34, No. 1.
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title = "Sodium Metabisulfite: Effects on Ionic Currents and Excitotoxicity",
abstract = "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.",
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Sodium Metabisulfite : Effects on Ionic Currents and Excitotoxicity. / Lai, Ming Chi; Hung, Te Yu; Lin, Kao Min; Sung, Pi-Shan; Wu, Shyh Jong; Yang, Chih Sheng; Wu, Yi-Jen; Tsai, Jing Jane; Wu, Sheng-Nan; Huang, Chin-Wei.

In: Neurotoxicity Research, Vol. 34, No. 1, 01.07.2018.

Research output: Contribution to journalArticle

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T1 - Sodium Metabisulfite

T2 - Effects on Ionic Currents and Excitotoxicity

AU - Lai, Ming Chi

AU - Hung, Te Yu

AU - Lin, Kao Min

AU - Sung, Pi-Shan

AU - Wu, Shyh Jong

AU - Yang, Chih Sheng

AU - Wu, Yi-Jen

AU - Tsai, Jing Jane

AU - Wu, Sheng-Nan

AU - Huang, Chin-Wei

PY - 2018/7/1

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