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The Journal of Neuroscience, March 15, 2003, 23(6):2069

Upregulation of the Hyperpolarization-Activated Cation Current after Chronic Compression of the Dorsal Root Ganglion

Hang Yao¹, David F. Donnelly², Chao Ma¹, and Robert H. LaMotte¹

Departments of ¹ Anesthesiology and ² Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510

A chronic compression of the DRG (CCD) produces cutaneous hyperalgesia and an enhanced excitability of neuronal somata in the compressed ganglion. The hyperpolarization-activated current (I_h), present in the somata and axons of DRG neurons, acts to induce a depolarization after a hyperpolarizing event and, if upregulated after CCD, may contribute to enhanced neuronal excitability. Whole-cell patch-clamp recordings were obtained from acutely dissociated, retrogradely labeled, cutaneous, adult rat DRG neurons of medium size. Neurons were dissociated from L₄ and L₅ control DRGs or DRGs that had each been compressed for 5-7 d by L-shaped rods inserted into the intervertebral foramina. I_h, consisting of a slowly activating inward current during a step hyperpolarization, was recorded from every labeled, medium-sized neuron and was blocked by 1 mM cesium or 15 µM ZD7288. Compared with control, CCD increased the current density and rate of activation significantly without changing its reversal potential, voltage dependence of activation, or rate of deactivation. Because I_h activation provides a depolarizing current to the neuron, thus enhancing neuronal excitability, our results are consistent with the hypothesis that I_h contributes to hyperalgesia after CCD-induced nerve injury.

Key words: hyperpolarization-activated current; I_h; ion channels; dorsal root ganglion compression; neuropathic pain; rats

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2362069-06$05.00/0

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