title: Alpha 2-adrenergic autoreceptors in A5 and A6 neurons of neonate rats.
abstract: A5 noradrenergic neurons control sympathetic outflow, nociception, and respiration. The presence of alpha 2-adrenergic receptors (alpha 2-ARs) in A5 cells has been suggested by immunohistochemistry. In the present experiments, we analyze the response of spinally projecting A5 cells to alpha 2-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 -55 mV, norepinephrine (NE) in the presence of the alpha 1-AR antagonist prazosin produced a Ba(2+)-sensitive outward current (20.4 +/- 2.6 pA; n = 28). The alpha 2-AR-induced current reversed at the K+ equilibrium potential (EK) at three different extracellular K+ 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 +/- 0.6 pA outward current). Pontospinal A6 neurons (n = 11) were also recorded. Six A6 cells displayed large tetrodotoxin (TTX)-resistant membrane oscillations. In these cells, the current induced by alpha 2-AR stimulation did not reverse over the voltages tested (-50 to -130 mV) or reversed at potentials more negative than EK (less than -114 mV). In A6 neurons that did not display large oscillations (n = 5), the alpha 2-AR-induced current reversed at or close to the EK (-90 +/- 1.6 mV). In conclusion, A5 cells, like locus ceruleus neurons, have alpha 2-ARs that may function as autoreceptors. In both cases, alpha 2-AR activation increases an inwardly rectifying K+ conductance. In A5 cells, we found no evidence that alpha 2-AR activation decreases a resting Na+ conductance. The inhibition of A5 cells by clonidine and other agents with alpha 2-AR agonist activity is likely to contribute to the ability of these drugs to decrease sympathetic tone and arterial pressure.
authors.affiliation: Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: D
authors.initials: D
authors.lastname: Huangfu
authors.forename: P G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000502:physiology*; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008536:Meglumine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D015221:Potassium Channels; D018341:Receptors, Adrenergic, alpha-2; D013779:Tetrodotoxin; D008536:Meglumine; D012964:Sodium; C058525:2-methoxyidazoxan; D011188:Potassium; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan