title: Vanilloids selectively sensitize thermal glutamate release from TRPV1 expressing solitary tract afferents.
abstract: Vanilloids, high temperature, and low pH activate the transient receptor potential vanilloid type 1 (TRPV1) receptor. In spinal dorsal root ganglia, co-activation of one of these gating sites on TRPV1 sensitized receptor gating by other modes. Here in rat brainstem slices, we examined glutamate synaptic transmission in nucleus of the solitary tract (NTS) neurons where most cranial primary afferents express TRPV1, but TRPV1 sensitization is unknown. Electrical shocks to the solitary tract (ST) evoked EPSCs (ST-EPSCs). Activation of TRPV1 with capsaicin (100 nM) increased spontaneous EPSCs (sEPSCs) but inhibited ST-EPSCs. High concentrations of the ultra-potent vanilloid resiniferatoxin (RTX, 1 nM) similarly increased sEPSC rates but blocked ST-EPSCs. Lowering the RTX concentration to 150 pM modestly increased the frequency of the sEPSCs without causing failures in the evoked ST-EPSCs. The sEPSC rate increased with raising bath temperature to 36 °C. Such thermal responses were larger in 150 pM RTX, while the ST-EPSCs remained unaffected. Vanilloid sensitization of thermal responses persisted in TTX but was blocked by the TRPV1 antagonist capsazepine. Our results demonstrate that multimodal activation of TRPV1 facilitates sEPSC responses in more than the arithmetic sum of the two activators, i.e. co-activation sensitizes TRPV1 control of spontaneous glutamate release. Since action potential evoked glutamate release is unaltered, the work provides evidence for cooperativity in gating TRPV1 plus a remarkable separation of calcium mechanisms governing the independent vesicle pools responsible for spontaneous and evoked release at primary afferents in the NTS.
authors.affiliation: Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR, USA. Electronic address: hofmannwfu@gmail.com.
authors.forename: Mackenzie E
authors.initials: ME
authors.lastname: Hofmann
authors.affiliation: Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Andresen
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D004224:Diterpenes; D018689:Sensory System Agents; D026941:Sodium Channel Blockers; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D018698:Glutamic Acid; D013779:Tetrodotoxin; C024353:resiniferatoxin; D002211:Capsaicin
keywords: Nucleus of the solitary tract; Resiniferatoxin; TRPV1