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

Abstract

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.

• Authors: S M Todorovic, V Jevtovic-Todorovic, A Meyenburg, S Mennerick, E Perez-Reyes, C Romano, J W Olney, C F Zorumski
• Journal: Neuron (Neuron) Vol. 31 Issue 1 Pg. 75-85 (Jul 19 2001) ISSN: 0896-6273 [Print] United States
• PMID: 11498052 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• Analysis of Variance
• Animals
• Calcium Channels, T-Type (chemistry, genetics, 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, physiology)
• Neurons (drug effects, physiology)
• Neurons, Afferent (drug effects, physiology)
• Nociceptors (physiology)
• Oxidation-Reduction
• Pain (physiopathology)
• Patch-Clamp Techniques
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (metabolism)
• Skin (innervation)
• Transfection