a2-Adrenergic autoreceptors in A5 and A6 neurons of neonate rats

Huangfu, Donghai, and Patrice G. Guyenet. a2Adrenergic autoreceptors in A5 and A6 neurons of neonate rats. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H2290– H2295, 1997.—A5 noradrenergic neurons control sympathetic outflow, nociception, and respiration. The presence of a2-adrenergic receptors (a2-ARs) in A5 cells has been suggested by immunohistochemistry. In the present experiments, we analyze the response of spinally projecting A5 cells to a2-AR agonists, and we compare it with that of locus ceruleus (A6) neurons. Whole cell recordings were obtained from 52 spinally projecting neurons in the ventrolateral pons of neonate rats. Immunohistochemistry showed that 60% of the recorded cells were A5 cells. In A5 cells clamped at 255 mV, norepinephrine (NE) in the presence of the a1-AR antagonist prazosin produced a Ba21-sensitive outward current (20.4 6 2.6 pA; n 5 28). The a2-AR-induced current reversed at the K1 equilibrium potential (EK) at three different extracellular K1 concentrations. Replacement of 82% of the extracellular Na concentration with N-methyl-D-glucamine did not change the reversal potential. The 19 presumably noncatecholaminergic neurons responded weakly or not at all to NE (2.5 6 0.6 pA outward current). Pontospinal A6 neurons (n 5 11) were also recorded. Six A6 cells displayed large tetrodotoxin (TTX)-resistant membrane oscillations. In these cells, the current induced by a2-AR stimulation did not reverse over the voltages tested (250 to 2130 mV) or reversed at potentials more negative than EK (less than 2114 mV). In A6 neurons that did not display large oscillations (n 5 5), the a2-AR-induced current reversed at or close to the EK (290 6 1.6 mV). In conclusion, A5 cells, like locus ceruleus neurons, have a2-ARs that may function as autoreceptors. In both cases, a2-AR activation increases an inwardly rectifying K1 conductance. In A5 cells, we found no evidence that a2-AR activation decreases a resting Na1 conductance. The inhibition of A5 cells by clonidine and other agents with a2-AR agonist activity is likely to contribute to the ability of these drugs to decrease sympathetic tone and arterial pressure.