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Mechanisms of facilitation of synaptic glutamate release by nicotinic agonists in the nucleus of the solitary tract

Mechanisms of facilitation of synaptic glutamate release by nicotinic agonists in the nucleus of... Abstract The nucleus of the solitary tract (NTS) is the principal integrating relay in the processing of visceral sensory information. Functional nicotinic acetylcholine receptors (nAChRs) have been found on presynaptic glutamatergic terminals in subsets of caudal NTS neurons. Activation of these receptors has been shown to enhance synaptic release of glutamate and thus may modulate autonomic sensory-motor integration and visceral reflexes. However, the mechanisms of nAChR-mediated facilitation of synaptic glutamate release in the caudal NTS remain elusive. This study uses rat horizontal brainstem slices, patch-clamp electrophysiology, and fluorescent Ca 2+ imaging to test the hypothesis that a direct Ca 2+ entrance into glutamatergic terminals through active presynaptic non-α7- or α7-nAChR-mediated ion channels is sufficient to trigger synaptic glutamate release in subsets of caudal NTS neurons. The results of this study demonstrate that, in the continuous presence of 0.3 μM tetrodotoxin, a selective blocker of voltage-activated Na + ion channels, facilitation of synaptic glutamate release by activation of presynaptic nAChRs (detected as an increase in the frequency of miniature excitatory postsynaptic currents) requires external Ca 2+ but does not require activation of presynaptic Ca 2+ stores and presynaptic high- and low-threshold voltage-activated Ca 2+ ion channels. Expanding the knowledge of mechanisms and pharmacology of nAChRs in the caudal NTS should benefit therapeutic approaches aimed at restoring impaired autonomic homeostasis. brainstem nicotinic acetylcholine receptors Copyright © 2011 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Cell Physiology The American Physiological Society

Mechanisms of facilitation of synaptic glutamate release by nicotinic agonists in the nucleus of the solitary tract

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References (59)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6143
eISSN
1522-1563
DOI
10.1152/ajpcell.00473.2010
pmid
21613611
Publisher site
See Article on Publisher Site

Abstract

Abstract The nucleus of the solitary tract (NTS) is the principal integrating relay in the processing of visceral sensory information. Functional nicotinic acetylcholine receptors (nAChRs) have been found on presynaptic glutamatergic terminals in subsets of caudal NTS neurons. Activation of these receptors has been shown to enhance synaptic release of glutamate and thus may modulate autonomic sensory-motor integration and visceral reflexes. However, the mechanisms of nAChR-mediated facilitation of synaptic glutamate release in the caudal NTS remain elusive. This study uses rat horizontal brainstem slices, patch-clamp electrophysiology, and fluorescent Ca 2+ imaging to test the hypothesis that a direct Ca 2+ entrance into glutamatergic terminals through active presynaptic non-α7- or α7-nAChR-mediated ion channels is sufficient to trigger synaptic glutamate release in subsets of caudal NTS neurons. The results of this study demonstrate that, in the continuous presence of 0.3 μM tetrodotoxin, a selective blocker of voltage-activated Na + ion channels, facilitation of synaptic glutamate release by activation of presynaptic nAChRs (detected as an increase in the frequency of miniature excitatory postsynaptic currents) requires external Ca 2+ but does not require activation of presynaptic Ca 2+ stores and presynaptic high- and low-threshold voltage-activated Ca 2+ ion channels. Expanding the knowledge of mechanisms and pharmacology of nAChRs in the caudal NTS should benefit therapeutic approaches aimed at restoring impaired autonomic homeostasis. brainstem nicotinic acetylcholine receptors Copyright © 2011 the American Physiological Society

Journal

AJP - Cell PhysiologyThe American Physiological Society

Published: Aug 1, 2011

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