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

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