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The Journal of Neuroscience, September 21, 2005, 25(38):8766-8775; doi:10.1523/JNEUROSCI.2527-05.2005

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Cellular/Molecular
The Endogenous Redox Agent L-Cysteine Induces T-Type Ca²+ Channel-Dependent Sensitization of a Novel Subpopulation of Rat Peripheral Nociceptors

Michael T. Nelson,^1,3 Pavle M. Joksovic,¹ Edward Perez-Reyes,^2,3 and Slobodan M. Todorovic^1,3

Departments of ¹Anesthesiology and ²Pharmacology and ³Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, Virginia 22908

Recent studies have demonstrated a previously unrecognized contribution of T-type Ca²⁺ channels in peripheral sensory neurons to pain sensation (nociception). However, the cellular mechanisms underlying the functions of these channels in nociception are not known. Here, in both acutely dissociated and intact rat dorsal root ganglion neurons, we characterize a novel subpopulation of capsaicin- and isolectin B₄-positive nociceptors that also expresses a high density of T-type Ca²⁺ currents. Using these "T-rich" cells as a model, we demonstrate that the endogenous reducing agent L-cysteine lowers the threshold for nociceptor excitability and induces burst firing by increasing the amplitude of T-type currents and shifting the gating parameters of T-type channels. These findings, which provide the first direct evidence of T-type Ca²⁺ channel involvement in the control of nociceptor excitability, suggest that endogenous T-type channel agonists may sensitize a unique subpopulation of peripheral nociceptors, consequently influencing pain processing under normal or pathological conditions.

Key words: low-threshold calcium channel; calcium; dorsal root ganglion; pain; thalamus; serotonin

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Received June 20, 2005; revised August 5, 2005; accepted August 5, 2005.

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