title: Thermally active TRPV1 tonically drives central spontaneous glutamate release.
abstract: Central synapses spontaneously release neurotransmitter at low rates. In the brainstem, cranial visceral afferent terminals in caudal solitary tract nucleus (NTS) display pronounced, activity-dependent, asynchronous release of glutamate and this extra release depends on TRPV1 receptors (TRPV1+). Asynchronous release is absent for afferents lacking TRPV1 (TRPV1-) and resting EPSC frequency was greater in TRPV1+. Here, we studied this basal activity difference by assessing thermal sensitivity of spontaneous and miniature synaptic events in TRPV1+ and TRPV1- second-order NTS neurons. The spontaneous EPSC rate decreased when temperature was decreased, increased steeply between 30 and 42°C only in TRPV1+ neurons, and was calcium-dependent. TRPV1-specific antagonist SB366791, but not TTX, strongly attenuated thermal responses. Temperature changes failed to alter EPSC frequency in TRPV1- neurons. EPSC amplitudes and decay kinetics changed little with temperature. IPSCs in these second-order NTS neurons were unaltered by temperature. Such results suggest that activated, presynaptic TRPV1+ receptors trigger continuous resting release of glutamate vesicles at physiological temperatures only in capsaicin-responsive terminals. In mechanically isolated individual neurons harvested from medial NTS, increases in temperature increased the rate of glutamate release only in TRPV1+ neurons, whereas IPSC rates were unaffected. Cadmium failed to block thermal increases in glutamate release, suggesting that calcium entry through TRPV1 channels may trigger glutamate release independently of voltage-activated calcium channels. Together, our findings indicate a new form of afferent signaling in which TRPV1 channels within central terminals of peripheral afferents tonically generate glutamate release in NTS at 37°C in the absence of afferent action potentials.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Shoudai
authors.forename: James H
authors.initials: JH
authors.lastname: Peters
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: McDougall
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Fawley
authors.forename: Michael C
authors.initials: MC
authors.lastname: Andresen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D019187:Cadmium Compounds / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013697:Thermosensing / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000813:Anilides; D019187:Cadmium Compounds; D002934:Cinnamates; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D026941:Sodium Channel Blockers; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C493922:Trpv1 protein, rat; D018698:Glutamic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D002211:Capsaicin; D002118:Calcium