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

Slobodan M. Todorovic, Vesna Jevtovic-Todorovic, Adam Meyenburg, Steven Mennerick, Edward Perez-Reyes, Carmelo Romano, John W. Olney, Charles F. Zorumski

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

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 Cav3.2 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) (DDNB) 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.

Original languageEnglish
Pages (from-to)75-85
Number of pages11
JournalNeuron
Volume31
Issue number1
DOIs
StatePublished - 2001

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