Thermally active TRPV1 tonically drives central spontaneous glutamate release.
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.
Shoudai
Kiyomitsu
K
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239, USA.
Peters
James H
JH
McDougall
Stuart J
SJ
Fawley
Jessica A
JA
Andresen
Michael C
MC
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
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