Redox modulation of T-type calcium channels in rat peripheral nociceptors

Neuron. 2001 Jul 19;31(1):75-85. doi: 10.1016/s0896-6273(01)00338-5.


Although T-type calcium channels were first described in sensory neurons, their function in sensory processing remains unclear. In isolated rat sensory neurons, we show that redox agents modulate T currents but not other voltage- and ligand-gated channels thought to mediate pain sensitivity. Similarly, redox agents modulate currents through Ca(v)3.2 recombinant channels. When injected into peripheral receptive fields, reducing agents, including the endogenous amino acid L-cysteine, induce thermal hyperalgesia. This hyperalgesia is blocked by the oxidizing agent 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) and the T channel antagonist mibefradil. DTNB alone and in combination with mibefradil induces thermal analgesia. Likewise, L-cysteine induces mechanical DTNB-sensitive hyperalgesia in peripheral receptive fields. These data strongly suggest a role for T channels in peripheral nociception. Redox sites on T channels in peripheral nociceptors could be important targets for agents that modify pain perception.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Calcium Channels, T-Type / chemistry
  • Calcium Channels, T-Type / genetics
  • Calcium Channels, T-Type / physiology*
  • Cell Line
  • Cells, Cultured
  • Cysteine / pharmacology
  • Dithionitrobenzoic Acid / pharmacology
  • Dithiothreitol / pharmacology
  • Female
  • Ganglia, Spinal / physiology*
  • Hot Temperature
  • Humans
  • Hyperalgesia / physiopathology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology*
  • Nociceptors / physiology*
  • Oxidation-Reduction
  • Pain / physiopathology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / metabolism
  • Skin / innervation
  • Transfection


  • Calcium Channels, T-Type
  • Recombinant Proteins
  • Dithionitrobenzoic Acid
  • Cysteine
  • Dithiothreitol