Effect of increasing temperature on TRPV1-mediated responses in isolated rat pulmonary sensory neurons.
Hyperthermia has been shown to sensitize vagal pulmonary C-fibers in anesthetized rats. However, it was not clear whether the effect was due to a direct action of hyperthermia on these sensory neurons. To answer this question, we carried out this study to determine the effect of increasing temperature on the responses to various chemical stimuli in isolated nodose and jugular ganglion neurons innervating the rat lungs. In the whole cell perforated patch-clamp study, when the temperature was increased from normal (approximately 36 degrees C) to hyperthermic (approximately 40.6 degrees C) level of the rat body temperature, the inward currents evoked by capsaicin, a selective activator of the transient receptor potential vanilloid type 1 (TRPV1), and 2-aminoethoxydiphenyl borate (2-APB), a nonselective activator of TRPV1-3 receptors, were both significantly increased. This potentiating effect was clearly present even at a moderate level of hyperthermia (approximately 39 degrees C). However, only the slow, sustained component of acid-evoked current mediated through the TRPV1 receptor was potentiated by hyperthermia, whereas the rapid, transient component was inhibited. In contrast, the currents evoked by adenosine 5'-triphosphate and acetylcholine, neither of which is known to activate the TRPV1 channel, did not increase when the same temperature elevation was applied. Furthermore, the hyperthermia-induced potentiation of the cell response to 2-APB was significantly attenuated by either capsazepine or AMG 9810, selective TRPV1 antagonists. In conclusion, increasing temperature within the physiological range exerts a potentiating effect on the response to TRPV1 activators in these neurons, which is probably mediated through a positive interaction between hyperthermia and these chemical activators at the TRPV1 channel.
Ni
Dan
D
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Lee
Lu-Yuan
LY
D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials; D018738:Hexamethonium / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D008168:Lung / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000502:physiology*; D013696:Temperature; D014630:Vagus Nerve / Q000502:physiology
C500530:3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide; D000178:Acrylamides; D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D018738:Hexamethonium; C109986:2-aminoethoxydiphenyl borate; C071423:capsazepine; D002211:Capsaicin