alpha(2)-adrenoceptor-mediated presynaptic inhibition in bulbospinal neurons of rostral ventrolateral medulla

The rostral ventrolateral medulla (RVLM) controls sympathetic tone via exci tatory bulbospinal neurons. It is also the main target of alpha(2)-adrenoce ptor (alpha(2)-AR) agonists' used for treatment of hypertension. In this st udy, we examined the synaptic mechanisms by which alpha(2)-AR agonists may inhibit the activity of RVLM bulbospinal neurons. We recorded selectively f rom RVLM bulbospinal neurons in brain stem slices of neonate rats (P5-P21) using the patch-clamp technique (holding potential -70 mV). alpha(2)-ARs we re activated by norepinephrine (NE, 30 mu M) in the presence of the alpha(1 )-adrenoceptor blocker prazosin. NE induced modest outward currents (5-28 p A) in 70% of the cells that were blocked by barium and by the alpha(2)-AR a ntagonist 2-methoxyidazoxan. The magnitude of this current was not correlat ed with the tyrosine hydroxylase immunoreactivity of the neurons. Mono- and oligosynaptic excitatory postsynaptic currents (EPSCs) or monosynaptic inh ibitory postsynaptic currents (IPSCs) were evoked by focal electrical stimu lation. In all cells, NE decreased the amplitude of the evoked EPSCs in the absence or presence of barium (49 and 70%) and decreased the amplitude of the evoked IPSCs (64 and 59%). The effect of NE on EPSC amplitude was block ed by 2-methoxyidazoxan. Focal stimulation produced a 1- to 2-s EPSC afterd ischarge (probably due to activation of interneurons) that was 53% inhibite d by NE. In the presence of tetrodotoxin, NE decreased the frequency of min iature EPSCs by 74%. In short, alpha(2)-AR stimulation produces weak postsy naptic responses in RVLM bulbospinal neurons and powerful presynaptic inhib ition of both glutamatergic and GABAergic inputs. Thus the inhibition of RV LM bulbospinal neurons by alpha(2)-AR agonists in vivo results from a combi nation of postsynaptic inhibition, disfacilitation, and disinhibition.