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Oxidation of extracellular cysteines by mercury chloride reduces TRPV1 activity in rat dorsal root ganglion neurons

  • Jin, Yun-Ju (Department of Physiology, Seoul National University College of Medicine) ;
  • Park, Jin-Young (Department of Physiology and Biophysics, Inha University College of Medicine) ;
  • Kim, Jun (Department of Physiology and Biophysics, Inha University College of Medicine) ;
  • Kwak, Ji-Yeon (Department of Physiology, Seoul National University College of Medicine)
  • Received : 2010.11.21
  • Accepted : 2010.12.02
  • Published : 2011.09.30

Abstract

Transient receptor potential vanilloid type 1 (TRPV1) receptor plays an important role as a molecular detector of noxious signals in primary sensory neurons. Activity of TRPV1 can be modulated by the change in the environment such as redox state and extracellular cations. In the present study, we investigated the effect of the mercury chloride ($HgCl_2$) on the activity of TRPV1 in rat dorsal root ganglia (DRG) neurons using whole-cell patch clamp technique. Extracellular $HgCl_2$ reversibly reduced the magnitudes of capsaicin-activated currents ($I_{cap}$) in DRG neurons in a dose-dependent manner. The blocking effect of $HgCl_2$ was prevented by pretreatment with the reducing agent dithiothreitol (DTT). Inhibition of $I_{cap}$ by $HgCl_2$ was abolished by point mutation of individual cysteine residues located on the extracellular surface of TRPV1. These results suggest that three extracellular cysteines of TRPV1, Cys616, Cys634 and Cys621, are responsible for the oxidative modulation of $I_{cap}$ by $HgCl_2$.

Keywords

References

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