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

• Published in: American Journal of Physiology: Cell Physiology Vol. 301; no. 2; pp. C347 - C361
• Main Authors: Kalappa, Bopanna I, Feng, Lin, Kem, William R, Gusev, Alexander G, Uteshev, Victor V
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2011
• Subjects: Acetylcholine receptors (nicotinic); alpha7 Nicotinic Acetylcholine Receptor; Animals; Autonomic nervous system; Brain; Brain slice preparation; Brain stem; Caffeine - pharmacology; Calcium; Calcium channels; Calcium imaging; Calcium Signaling - drug effects; Electrophysiology; Excitatory Postsynaptic Potentials; Glutamatergic transmission; Glutamic acid; Glutamic Acid - metabolism; Homeostasis; In Vitro Techniques; Information processing; Integration; Ion channels; Ions; Mecamylamine - pharmacology; Membrane Transporters, Ion Channels and Pumps; Microscopy, Fluorescence; Neurons; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Nicotinic Antagonists - pharmacology; Patch-Clamp Techniques; Pharmacology; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - metabolism; Sensory integration; Sodium Channel Blockers - pharmacology; Solitary Nucleus - drug effects; Solitary Nucleus - metabolism; Solitary tract nucleus; Synaptic Transmission - drug effects; T cell receptors; Temperature; Tetrodotoxin - pharmacology; Time Factors
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00473.2010

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.