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2 Adrenergic Receptors
1 Anesthesiology, Penn State Univ, Hershey, PA, USA
* To whom correspondence should be addressed. E-mail: hpan{at}psu.edu.
Neurons in the paraventricular nucleus (PVN) that project to the brainstem and spinal cord are important for autonomic regulation. The excitability of pre-autonomic PVN neurons is controlled by the noradrenergic input from the brainstem. In this study, we determined the role of 
2 adrenergic receptors in the regulation of excitatory and inhibitory synaptic inputs to spinally projecting PVN neurons. Postsynaptic currents were recorded using whole-cell voltage-clamp techniques on PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Application of 5-20 µM clonidine, an 2 receptor agonist, significantly reduced the amplitude of evoked GABAergic IPSCs in a dose-dependent manner. Also, 10 µM clonidine significantly decreased the frequency (from 2.68±0.41 to 1.22 ±0.40 Hz) but not the amplitude of mIPSCs and this effect was blocked by the 2 receptor antogonist yohimbine. Furthermore, clonidine increased the paired-pulse ratio of evoked IPSCs from 1.25±0.05 to 1.61±0.08 (P < 0.05). On the other hand, clonidine had little effect on evoked glutamatergic EPSCs, mEPSCs, and the paired-pulse ratio of evoked EPSCs in most cells examined. Additionally, double immunofluorescence labeling revealed that the 2A receptor and GABA immunoreactivities were colocalized in close apposition to labeled PVN neurons. Collectively, these data suggest that stimulation of 2 adrenergic receptors primarily attenuates GABAergic inputs to PVN output neurons to the spinal cord. The presynaptic 2 receptors function as heterorecptors to modulate synaptic GABA release and contribute to the hypothalamic regulation of sympathetic outflow.
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