Ectopic α2-Adrenoceptors Couple to N-Type Ca2+Channels in Axotomized Rat Sensory Neurons

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Abstract
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 μm) activated β-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 α2-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.