Inhibitory action of thimerosal, a sulfhydryl oxidant, on sodium channels in rat sensory neurons.
The effects of thimerosal, a sulfhydryl oxidizing agent, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons were studied using the whole-cell patch clamp technique. Thimerosal blocked the two types of sodium channels in a dose-dependent manner. The inhibitory effect of thimerosal was much more pronounced in TTX-R sodium channels than TTX-S sodium channels. The effect of thimerosal was irreversible upon wash-out with thimerosal-free external solution. However, dithiothreitol, a reducing agent, partially reversed it. Thimerosal shifted the steady-state inactivation curves for both types of sodium channels in the hyperpolarizing direction. The voltage dependence of activation of both types of sodium channels was shifted in the depolarizing direction by thimerosal. The inactivation rate in both types of sodium channels increased after thimerosal treatment. All these effects of thimerosal would add up to cause a depression of sodium channel function leading to a diminished neuronal excitability.
Song
J
J
Department of Pharmacology, Chung-Ang University, College of Medicine, 221 Heuk-Suk Dong, Dong-Jak Ku, Seoul, South Korea. jinhosdragonar.nm.cau.ac.kr
Jang
Y Y
YY
Shin
Y K
YK
Lee
M Y
MY
Lee
C
C
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D013849:Thimerosal / Q000494:pharmacology*; D013997:Time Factors
D062556:NAV1.7 Voltage-Gated Sodium Channel; D009479:Neuropeptides; D016877:Oxidants; D011310:Preservatives, Pharmaceutical; C503480:Scn9a protein, rat; D015222:Sodium Channels; D013438:Sulfhydryl Compounds; D013849:Thimerosal; D013779:Tetrodotoxin; D004229:Dithiothreitol