Redox modulation of T-type calcium channels in rat peripheral nociceptors.
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.
Todorovic
S M
SM
Department of Anesthesiology, Washington University School of Medicine, 63110, St Louis, MO, USA. todorovs@msnotes.wustl.edu
Jevtovic-Todorovic
V
V
Meyenburg
A
A
Mennerick
S
S
Perez-Reyes
E
E
Romano
C
C
Olney
J W
JW
Zorumski
C F
CF
D000704:Analysis of Variance; D000818:Animals; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D010084:Oxidation-Reduction; D010146:Pain / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000294:innervation; D014162:Transfection
D020747:Calcium Channels, T-Type; D011994:Recombinant Proteins; D004228:Dithionitrobenzoic Acid; D003545:Cysteine; D004229:Dithiothreitol