Alpha2-adrenoceptor-mediated presynaptic inhibition in bulbospinal neurons of rostral ventrolateral medulla.
The rostral ventrolateral medulla (RVLM) controls sympathetic tone via excitatory bulbospinal neurons. It is also the main target of alpha2-adrenoceptor (alpha2-AR) agonists used for treatment of hypertension. In this study, we examined the synaptic mechanisms by which alpha2-AR agonists may inhibit the activity of RVLM bulbospinal neurons. We recorded selectively from RVLM bulbospinal neurons in brain stem slices of neonate rats (P5-P21) using the patch-clamp technique (holding potential -70 mV). alpha2-ARs were activated by norepinephrine (NE, 30 microM) in the presence of the alpha1-adrenoceptor blocker prazosin. NE induced modest outward currents (5-28 pA) in 70% of the cells that were blocked by barium and by the alpha2-AR antagonist 2-methoxyidazoxan. The magnitude of this current was not correlated with the tyrosine hydroxylase immunoreactivity of the neurons. Mono- and oligosynaptic excitatory postsynaptic currents (EPSCs) or monosynaptic inhibitory postsynaptic currents (IPSCs) were evoked by focal electrical stimulation. 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 blocked by 2-methoxyidazoxan. Focal stimulation produced a 1- to 2-s EPSC afterdischarge (probably due to activation of interneurons) that was 53% inhibited by NE. In the presence of tetrodotoxin, NE decreased the frequency of miniature EPSCs by 74%. In short, alpha2-AR stimulation produces weak postsynaptic responses in RVLM bulbospinal neurons and powerful presynaptic inhibition of both glutamatergic and GABAergic inputs. Thus the inhibition of RVL bulbospinal neurons by alpha2-AR agonists in vivo results from a combination of postsynaptic inhibition, disfacilitation, and disinhibition.
Hayar
A
A
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
Guyenet
P G
PG
D000818:Animals; D001933:Brain Stem / Q000502:physiology; D008526:Medulla Oblongata / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D018341:Receptors, Adrenergic, alpha-2