Inhibitory action of thimerosal, a sulfhydryl oxidant, on sodium channels in rat sensory neurons

The effects of thimerosal, a sulfhydryl oxidizing agent, on tetrodotoxin-se nsitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat d orsal root ganglion neurons were studied using the whole-cell patch clamp t echnique. Thimerosal blocked the two types of sodium channels in a dose-dep endent manner. The inhibitory effect of thimerosal was much more pronounced in TTX-R sodium channels than TTX-S sodium channels. The effect of thimero sal was irreversible upon wash-out with thimerosal-free external solution. However, dithiothreitol, a reducing agent, partially reversed it. Thimerosa l shifted the steady-state inactivation curves for both types of sodium cha nnels in the hyperpolarizing direction. The voltage dependence of activatio n of both types of sodium channels was shifted in the depolarizing directio n by thimerosal. The inactivation rate in both types of sodium channels inc reased after thimerosal treatment. All these effects of thimerosal would ad d up to cause a depression of sodium channel function leading to a diminish ed neuronal excitability. (C) 2000 Elsevier Science B.V. All rights reserve d.