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Papers of the Week

Papers: 24 Sep 2022 - 30 Sep 2022

Animal Studies

2022 Sep 26

Mol Pain

T-type Ca2+ channels play a dual role in modulating the excitability of dorsal root ganglia neurons.


A subgroup of low-threshold dorsal root ganglia (DRG) neurons discharge action potentials (APs) with an afterdepolarizing potential (ADP). The ADP is formed by T-type Ca2+ currents. It is known that T-type Ca2+ currents contribute to neuropathic pain. However, the change in ADP-firing of injured DRG neurons has not been widely studied yet. Here we applied patch clamp to record ADP-firing and T-type Ca2+ currents in intact and chronically compressed DRG (CCD) neurons and examined T-type Ca2+ channel proteins expression with western blotting. After CCD injury, the incidences of both ADP firing and non-ADP burst firing increased, and T-type Ca2+ channels contributed to both of these firing patterns. The neurons discharging large-amplitude-ADP firing were TTX-insensitive, implying that high-density T-type Ca2+ channels might cooperate with TTX-insensitive Na+ channels to reduce the AP threshold. By contrast, the neurons displaying non-ADP burst firing were TTX-sensitive, implying that low density T-type Ca2+ channels may cooperate with TTX-sensitive Na+ channels to increase AP number. In DRG neurons, T-type Ca2+ currents density varied widely, ranging between 100 pA/pF and 5 pA/pF. After injury, the proportion of DRG neurons with large T-type Ca2+ currents increased in parallel with the increase in the incidence of large-amplitude-ADP firing. And in addition to Cav3.2, Cav3.3 channels are also likely to contribute to low-threshold firing. The data revealed that T-type Ca2+ channels may play a dual role in modulating the injured neurons' high excitability through a cooperative process with Na+ channels, thereby contributing to neuropathic pain.