Upregulation of the hyperpolarization-activated cation current after chronic compression of the dorsal root ganglion.
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 microm 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.
Yao
Hang
H
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Donnelly
David F
DF
Ma
Chao
C
LaMotte
Robert H
RH
D000818:Animals; D002469:Cell Separation; D048429:Cell Size; D002586:Cesium / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000503:physiopathology*; D006930:Hyperalgesia / Q000209:etiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008959:Models, Neurological; D009408:Nerve Compression Syndromes / Q000150:complications / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011743:Pyrimidines; C082246:ICI D2788; D002586:Cesium