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5-HT 3 R-sourced calcium enhances glutamate release from a distinct vesicle pool.
- Source :
-
Brain research [Brain Res] 2019 Oct 15; Vol. 1721, pp. 146346. Date of Electronic Publication: 2019 Jul 23. - Publication Year :
- 2019
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Abstract
- The serotonin 3 receptor (5-HT <subscript>3</subscript> R) is a calcium-permeant channel heterogeneously expressed in solitary tract (ST) afferents. ST afferents synapse in the nucleus of the solitary tract (NTS) and rely on a mix of voltage-dependent calcium channels (CaVs) to control synchronous glutamate release (ST-EPSCs). CaV activation triggers additional, delayed release of glutamate (asynchronous EPSCs) that trails after the ST-EPSCs but only from afferents expressing the calcium-permeable, transient receptor potential vanilloid type 1 receptor (TRPV1). Most afferents express TRPV1 and have high rates of spontaneous glutamate release (sEPSCs) that is independent of CaVs. Here, we tested whether 5-HT <subscript>3</subscript> R-sourced calcium contributes to these different forms of glutamate release in horizontal NTS slices from rats. The 5-HT <subscript>3</subscript> R selective agonist, m-chlorophenyl biguanide hydrochloride (PBG), enhanced sEPSCs and/or delayed the arrival times of ST-EPSCs (i.e. increased latency). The specific 5-HT <subscript>3</subscript> R antagonist, ondansetron, attenuated these effects consistent with direct activation of 5-HT <subscript>3</subscript> Rs. PBG did not alter ST-EPSC amplitude or asynchronous EPSCs. These independent actions suggest two distinct 5-HT <subscript>3</subscript> R locations; axonal expression that impedes conduction and terminal expression that mobilizes a spontaneous vesicle pool. Calcium chelation with EGTA-AM attenuated the frequency of 5-HT <subscript>3</subscript> R-activated sEPSCs by half. The mixture of chelation-sensitive and resistant sEPSCs suggests that 5-HT <subscript>3</subscript> R-activated vesicles span calcium diffusion distances that are both distal (micro-) and proximal (nanodomains) to the channel. Our results demonstrate that the calcium domains of 5-HT <subscript>3</subscript> Rs do not overlap other calcium sources or their respective vesicle pools. 5-HT <subscript>3</subscript> Rs add a unique calcium source on ST afferents as part of multiple independent synaptic signaling mechanisms.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Action Potentials physiology
Animals
Capsaicin pharmacology
Excitatory Postsynaptic Potentials drug effects
Male
Neurons metabolism
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Serotonin metabolism
Solitary Nucleus drug effects
Synapses metabolism
Synaptic Transmission physiology
TRPV Cation Channels metabolism
Calcium metabolism
Glutamic Acid metabolism
Receptors, Serotonin, 5-HT3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1721
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 31348913
- Full Text :
- https://doi.org/10.1016/j.brainres.2019.146346