Abstract Title:

Regulation of sodium currents through oxidation and reduction of thiol residues.

Abstract Source:

Neuroscience. 2000 ;101(1):229-36. PMID: 11068151

Abstract Author(s):

J R Evans, K Bielefeldt

Article Affiliation:

J R Evans


Changes in redox state are involved in several physiological and pathophysiological processes. Previous experiments have demonstrated that nitric oxide can function as a reactive oxygen species, inhibiting neuronal sodium currents by nitrosylation of thiol residues. We hypothesized that nitric oxide and thiol oxidizers similarly modulate voltage-dependent sodium currents. Voltage-dependent sodium currents were studied with the whole-cell patch-clamp technique in NB41A3 neuroblastoma cells. The nitric oxide donor 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine did not affect sodium currents. In contrast, the thiol oxidizers thimerosal and 4,4'-dithiopyridine significantly inhibited sodium currents. The effect of thimerosal persisted after washout, but could be fully reversed by the reducing agent dithiothreitol. Reduced glutathione did not restore the sodium current amplitude when given extracellularly, while intracellular glutathione prevented the inhibitory effect of thimerosal. Pretreatment with the alkylating agent N-ethylmaleimide blocked the inhibitory action of thimerosal. Thiol oxidation caused a shift in the voltage dependence of fast and slow inactivation to more hyperpolarized potentials without concomitant effects on the voltage dependence of activation. Mercaptoethanol and reduced glutathione enhanced sodium currents by shifting the voltage dependence of inactivation to depolarized potentials. These results demonstrate that the oxidation and reduction of thiol residues alters the properties of voltage-sensitive sodium channels and may play an important role in the regulation of membrane excitability.

Study Type : In Vitro Study
Additional Links
Problem Substances : Thimerosal : CK(799) : AC(190)
Adverse Pharmacological Actions : Excitotoxic : CK(40) : AC(10)

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