Article

The endogenous redox agent L-cysteine induces T-type Ca2+ channel-dependent sensitization of a novel subpopulation of rat peripheral nociceptors

Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 10/2005; 25(38):8766-75. DOI: 10.1523/JNEUROSCI.2527-05.2005
Source: PubMed

ABSTRACT 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.

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    • "T-type calcium channels are primarily found in scattered small and medium sized DRG neurons, whereas the extremely large neurons do not express these channels [18]. Recent studies indicate that T-type calcium channels play an important role in regulating cellular excitability [19] [20]. Several pharmacological blockers and modulators of T-type calcium channels can ease neuropathic pain in a chronic constriction injury model [21]. "
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    • "Acutely isolated DRG neurons DRG cells from adolescent rats were prepared as previously described (Todorovic et al. 1998; Nelson et al. 2005; Choe et al. 2011). For recording, cells were plated onto uncoated glass coverslips, placed in a culture dish, and perfused with external solution. "
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    • "Functional expression of different Cav3 channels may influence Ca2+ signaling associated with different neuronal activities due to specific biophysical properties of these channels. Cav3.2 channels were shown to be underlying after depolarization potentials and participating in rebound discharge in medium [25] and T-rich [49] DRG neurons. However, relatively fast inactivation and slow recovery from inactivation limit the ability of Cav3.2 channels to respond to high frequency stimulation (>20 Hz). "
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