Thermal sensitivity of isolated vagal pulmonary sensory neurons: role of transient receptor potential vanilloid receptors

Abstract

A recent study has demonstrated that increasing the intrathoracic temperature from 36 degrees C to 41 degrees C induced a distinct stimulatory and sensitizing effect on vagal pulmonary C-fiber afferents in anesthetized rats (J Physiol 565: 295-308, 2005). We postulated that these responses are mediated through a direct activation of the temperature-sensitive transient receptor potential vanilloid (TRPV) receptors by hyperthermia. To test this hypothesis, we studied the effect of increasing temperature on pulmonary sensory neurons that were isolated from adult rat nodose/jugular ganglion and identified by retrograde labeling, using the whole cell perforated patch-clamping technique. Our results showed that increasing temperature from 23 degrees C (or 35 degrees C) to 41 degrees C in a ramp pattern evoked an inward current, which began to emerge after exceeding a threshold of approximately 34.4 degrees C and then increased sharply in amplitude as the temperature was further increased, reaching a peak current of 173 +/- 27 pA (n = 75) at 41 degrees C. The temperature coefficient, Q10, was 29.5 +/- 6.4 over the range of 35-41 degrees C. The peak inward current was only partially blocked by pretreatment with capsazepine (Delta I = 48.1 +/- 4.7%, n = 11) or AMG 9810 (Delta I = 59.2 +/- 7.8%, n = 8), selective antagonists of the TRPV1 channel, but almost completely abolished (Delta I = 96.3 +/- 2.3%) by ruthenium red, an effective blocker of TRPV1-4 channels. Furthermore, positive expressions of TRPV1-4 transcripts and proteins in these neurons were demonstrated by RT-PCR and immunohistochemistry experiments, respectively. On the basis of these results, we conclude that increasing temperature within the normal physiological range can exert a direct stimulatory effect on pulmonary sensory neurons, and this effect is mediated through the activation of TRPV1, as well as other subtypes of TRPV channels.

Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-α in rat pulmonary sensory neurons

“…DiI was initially sonicated, dissolved in ethanol, and diluted in saline (1% ethanol vol/vol). Our (25,41) previous studies have shown that after Ͼ7 days, the soma of pulmonary sensory neurons located in the vagal sensory ganglia were labeled with DiI.…”

“…and inhaled chemical irritants (e.g., acrolein, toluene diisocyanate, etc.) (7,25,41,46). Immunohistochemical studies have shown that TRPV1 channels are also colocalized with certain sensory neuropeptides, such as tachykinins and CGRP, in the sensory terminals (51).…”

Prostaglandin E2 enhances the sensitizing effect of hyperthermia on pulmonary C-fibers in rats

“…These data strongly suggest the involvement of TRPV1 as well as other subtypes of temperature-sensitive TRPV channels in the responses of these neurons to hyperthermia. In addition, the expressions of TRPV1-4 channel transcripts and proteins, respectively, in vagal pulmonary sensory neurons were further demonstrated in the reverse transcriptasepolymerase chain reaction and immunohistochemistry studies (Ni et al, 2006).…”

“…In fact, expression of the TRPV1 receptors on the sensory terminals has been considered one of the most distinct characteristic features of the pulmonary C-fiber afferents (Ho et al, 2001), although the temperature threshold for activating the TRPV1 (> 43°C) exceeds the physiological range of body temperature that was applied in our studies. To test this possibility, a follow-up study was recently carried out in isolated rat vagal pulmonary sensory neurons (Ni et al, 2006). Results of that study clearly showed that cultured jugular and nodose pulmonary sensory neurons can be directly activated by an increase in temperature within the normal physiological range.…”

Is TRPV1 a useful target in respiratory diseases?

“…In addition, TRPV1-4 channel mRNA and protein expression was evident in these neurons. This indicates that TRPV1, as well as other thermo-sensitive TRPV channel subtypes, are activated within the normal physiological range and play a primary role in regulating the response of pulmonary sensory neurons to hyperthermia [56]. However, the relative contributions of these different TRPV channel subtypes to the thermal sensitivity of these neurons remain to be determined, and the effects of these neurons' activation under normal or pathophysiological condition await future studies.…”