Ectopic alpha2-adrenoceptors couple to N-type Ca2+ channels in axotomized rat sensory neurons.
Dorsal root ganglion (DRG) neurons from control rats or from rats in which the sciatic nerve had been sectioned were studied by whole-cell recording techniques. Noradrenaline (10-100 micro;M) activated beta-adrenoceptors and increased L-type Ca2+ channel current in control DRG cells, but this had little effect on excitability (the number of action potentials generated by a pulse of current at rheobasic strength). By contrast, in cells from nerve-damaged animals, noradrenaline activated alpha2-adrenoceptors, suppressed N-type Ca2+ channel current, and increased excitability. In axotomized cells, it also reduced total outward current recorded at +70 mV. Because noradrenaline did not affect total outward current recorded in the presence of the Ca2+ channel blocker Cd2+ (0. 5-1 mM), its effects on excitability may result from reduction of Ca2+-sensitive K+-conductance(s) following suppression of N-type Ca2+ channel current. The strongest effects of noradrenaline were seen in small cells and in cells from animals that exhibited autotomy, a self-mutilatory behavior that can accompany peripheral nerve damage. Because many of these small DRG cells may be involved in the transmission of nociceptive information, changes in coupling between Ca2+ channels and adrenoceptors may contribute to the generation of the ectopic sensory nerve activity that has been implicated in the etiology of neuropathic pain.
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Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Smith
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D003714:Denervation; D005727:Ganglia, Spinal / Q000473:pathology; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012584:Sciatic Nerve / Q000293:injuries; D012652:Self Mutilation
D015220:Calcium Channels; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D002104:Cadmium; D002118:Calcium; D009638:Norepinephrine