Ectopic a2-Adrenoceptors Couple to N-Type Ca 21 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 mM) activated b-adrenoceptors and increased L-type Ca 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 nervedamaged animals, noradrenaline activated a2-adrenoceptors, suppressed N-type Ca channel current, and increased excitability. In axotomized cells, it also reduced total outward current recorded at 170 mV. Because noradrenaline did not affect total outward current recorded in the presence of the Ca channel blocker Cd (0.5–1 mM), its effects on excitability may result from reduction of Ca-sensitive K-conductance(s) following suppression of N-type Ca 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 Ca channels and adrenoceptors may contribute to the generation of the ectopic sensory nerve activity that has been implicated in the etiology of neuropathic pain.