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Angiotensin II stimulates spinally projecting paraventricular neurons through presynaptic disinhibition.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2003 Jun 15; Vol. 23 (12), pp. 5041-9. - Publication Year :
- 2003
-
Abstract
- Paraventricular nucleus (PVN) neurons that project to the spinal cord are important in the control of sympathetic outflow. Angiotensin II (Ang II) can stimulate PVN neurons, but its cellular mechanisms are not clear. In this study, we determined the effect of Ang II on the excitatory and inhibitory synaptic inputs to spinally projecting PVN neurons. Whole-cell patch-clamp recordings were performed on PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Immunocytochemistry labeling revealed that the immunoreactivity of angiotensin type 1 (AT1) receptors was colocalized with a presynaptic marker, synaptophysin, in the PVN. Application of 0.1-5 microm Ang II significantly decreased the amplitude of evoked GABAergic IPSCs in a concentration-dependent manner. Also, Ang II decreased the frequency of miniature IPSCs from 2.56 +/- 0.45 to 1.05 +/- 0.20 Hz (p < 0.05; n = 12), without affecting the amplitude and the decay time constant. The effect of Ang II on miniature IPSCs was blocked by losartan but not PD123319. However, Ang II had no effect on the evoked glutamatergic EPSCs and did not alter the frequency and amplitude of miniature EPSCs at concentrations that attenuated IPSCs. Furthermore, Ang II increased the firing rate of PVN neurons from 3.75 +/- 0.36 to 7.89 +/- 0.85 Hz (p < 0.05; n = 9), and such an effect was abolished by losartan. In addition, Ang II failed to excite PVN neurons in the presence of bicuculline. Thus, this study provides substantial new evidence that Ang II excites spinally projecting PVN neurons by attenuation of GABAergic synaptic inputs through activation of presynaptic AT1 receptors.
- Subjects :
- Action Potentials drug effects
Action Potentials physiology
Angiotensin Receptor Antagonists
Animals
Excitatory Postsynaptic Potentials drug effects
Excitatory Postsynaptic Potentials physiology
Female
GABA Antagonists pharmacology
Imidazoles pharmacology
Immunohistochemistry
In Vitro Techniques
Losartan pharmacology
Male
Neural Inhibition physiology
Neurons cytology
Neurons physiology
Paraventricular Hypothalamic Nucleus cytology
Paraventricular Hypothalamic Nucleus physiology
Patch-Clamp Techniques
Presynaptic Terminals physiology
Pyridines pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin biosynthesis
Receptors, Angiotensin drug effects
Spinal Cord cytology
Spinal Cord physiology
Synaptophysin biosynthesis
gamma-Aminobutyric Acid metabolism
Angiotensin II pharmacology
Neural Inhibition drug effects
Neurons drug effects
Paraventricular Hypothalamic Nucleus drug effects
Presynaptic Terminals drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 23
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 12832527