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Decreased A--type potassium current mediates the hyperexcitability of nociceptive neurons in the chronically compressed dorsal root ganglia

Yan Ni, Li Xiaohan, Cheng Qi, Yan Jin, Ni Xin, Sun Jihu

Department of Physiology,Department of Psychology,the Second Military Medical University.Shanghai 200433

Abstract

The excitability of nociceptive neurons increases in the intact dorsal root ganglion (DRG) after a chronic compression, but the underlying mechanisms are still unclear. The aim of this study was to investigate the ionic mechanisms underlying the hyperexcit-ability of nociceptive neurons in the compressed ganglion. Chronic compression of DRG (CCD) was produced in adult rats by inserting two rods through the intervertebral foramina to compress the L4 DRG and the ipsilateral L5 DRG. After 5-7 d, DRG somata were dissociated and placed in culture for 12-18 h. In sharp electrode recording model, we examined the lower current threshold and the depolarized membrane potential in the acutely dissociated CCD neurons, which are indication of hyperexcitability that is intrinsic to the soma. Since voltage-gated K~(+) (Kv) channels in primary sensory neurons are important for regulation of neuronal excitability, we hypothesized that CCD would alter K~(+) current properties in primary sensory neurons. We examined the effects of 4-aminopyridine (4-AP), a specific antagonist of A-type potassium channel, on the excitability of the control DRG neurons. With 4-AP in the external solution, the control DRG neurons depolarized (with discharges in some cells) and decreased their current threshold as the CCD neurons demonstrated, indicating the involvement of decreased A-type potassium current in the hyperexcitability of the injured neurons. Furthermore, the alteration of A-type potassium current in nociceptive neurons in the compressed ganglion was investigated with the whole-cell patch-clamp recording model. CCD significantly decreased A-type potassium current density in nociceptive DRG neurons. These data suggest that a reduction in A-type potassium currents contributes, at least in part, to the increase in neuron excitability that may lead to the development of pain and hyperalgesia associated with CCD.

Key words: Potassium channel;Dorsal root ganglion;Excitability;pain

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Citing This Article：

Yan Ni, Li Xiaohan, Cheng Qi, Yan Jin, Ni Xin, Sun Jihu. Decreased A--type potassium current mediates the hyperexcitability of nociceptive neurons in the chronically compressed dorsal root ganglia. Acta Physiol Sin 2007; 59 (2): 240-246 (in Chinese with English abstract).