Regulation of synaptic inputs to paraventricular-spinal output neurons by alpha2 adrenergic receptors.
Neurons in the paraventricular nucleus (PVN) that project to the brain stem and spinal cord are important for autonomic regulation. The excitability of preautonomic PVN neurons is controlled by the noradrenergic input from the brain stem. In this study, we determined the role of alpha(2) adrenergic receptors in the regulation of excitatory and inhibitory synaptic inputs to spinally projecting PVN neurons. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) 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. Bath application of 5-20 muM clonidine, an alpha(2) receptor agonist, significantly reduced the amplitude of evoked GABAergic IPSCs in a dose-dependent manner. Also, 10 microM clonidine significantly decreased the frequency (from 2.68 +/- 0.41 to 1.22 +/- 0.40 Hz) but not the amplitude of miniature IPSCs (mIPSCs), and this effect was blocked by the alpha(2) receptor antagonist 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 labeled cells examined. Additionally, immunofluorescence labeling revealed that the alpha(2A) receptor and GABA immunoreactivities were co-localized in close apposition to labeled PVN neurons. Collectively, these data suggest that stimulation of alpha(2) adrenergic receptors primarily attenuates GABAergic inputs to PVN output neurons to the spinal cord. The presynaptic alpha(2) receptors function as heteroreceptors to modulate synaptic GABA release and contribute to the hypothalamic regulation of sympathetic outflow.
Li
De-Pei
DP
Department of Anesthesiology, H187, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033-0850, USA. hpan@psu.edu
Atnip
Lindsay M
LM
Chen
Shao-Rui
SR
Pan
Hui-Lin
HL
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001933:Brain Stem / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005455:Fluorescent Antibody Technique / Q000379:methods; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018341:Receptors, Adrenergic, alpha-2; D016708:Synaptophysin; D015016:Yohimbine; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003000:Clonidine; D001640:Bicuculline