TRPA1 Channels Modify TRPV1-Mediated Current Responses in Dorsal Root Ganglion Neurons

Abstract

The transient receptor potential vanilloid 1 (TRPV1) channel is highly expressed in a subset of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia of experimental animals, responsible for nociception. Many researches have revealed that some TRPV1-positive neurons co-express the transient receptor potential ankyrin 1 (TRPA1) channel whose activities are closely modulated by TRPV1 channel. However, it is less investigated whether the activities of TRPV1 channel are modulated by the presence of TRPA1 channel in primary sensory neurons. This study clarified the difference in electrophysiological responses induced by TRPV1 channel activation between TRPA1-positive and TRPA1-negative DRG. TRPV1 and TRPA1 channel activations were evoked by capsaicin (1 μM), a TRPV1 agonist, and allyl isothiocyanate (AITC; 500 μM), a TRPA1 agonist, respectively. Capsaicin perfusion for 15 s caused a large inward current without a desensitization phase at a membrane potential of −70 mV in AITC-insensitive DRG (current density; 29.6 ± 5.6 pA/pF, time constant of decay; 12.8 ± 1.8 s). The capsaicin-induced currents in AITC-sensitive DRG had a small current density (12.7 ± 2.9 pA/pF) with a large time constant of decay (24.3 ± 5.4 s). In calcium imaging with Fura-2, the peak response by capsaicin was small and duration reaching the peak response was long in AITC-sensitive neurons. These electrophysiological differences were completely eliminated by HC-030031, a TRPA1 antagonist, in an extracellular solution or 10 mM EGTA, a Ca2+ chelator, in an internal solution. Capsaicin perfusion for 120 s desensitized the inward currents after a transient peak. The decay during capsaicin perfusion was notably slow in AITC-sensitive DRG; ratio of capsaicin-induced current 60 s after the treatment per the peak current in AITC-sensitive neurons (78 ± 9%) was larger than that in AITC-insensitive neurons (48 ± 5%). The capsaicin-induced current in the desensitization phase was attenuated by HC-030031 in AITC-insensitive DRG. These results indicate that (1) TRPV1-mediated currents in TRPA1-positive neurons characterize small current densities with slow decay, which is caused by TRPA1 channel activities and intracellular Ca2+ mobilization and (2) desensitization of TRPV1-mediated current in TRPA1-positive neurons is apparently slow, due to appending TRPA1-mediated current.

Antagonism of Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Trigeminal Neuropathic Pain: Study in an Animal Model

“…Moreover, we can also speculate that since TRPA1 and TRPV1 functions may be influenced by each other [ 20 , 86 , 87 ], a re-organization in the expression and nature of these channels after nerve injury [ 88 , 89 , 90 ] enabled ADM_12 to modulate TRPV1 channels as well. Although a physical interaction between these two channels may be questionable, even if some studies described it in vitro [ 19 , 21 ], many studies reported a functional interaction between them [ 20 , 86 , 91 , 92 , 93 ].…”

Sensory neuronal sensitisation occurs through HMGB-1–RAGE and TRPV1 in high-glucose conditions

“…TRPA1 is also sensitised in rat DRG immortalised neurons (50B11) in high-glucose conditions in vitro ( Hulse et al, 2015 ) and in animal models of diabetes. TRPA1 forms complexes with TRPV1, and can affect TRPV1 function, such as reducing desensitisation, thus potentially altering Ca 2+ responses ( Masuoka et al, 2017 ; Staruschenko et al, 2010 ). There is, however, no evidence that RAGE can directly alter TRPA1 function.…”

Receptor Mechanisms Mediating the Pro-Nociceptive Action of Hydrogen Sulfide in Rat Trigeminal Neurons and Meningeal Afferents

“…Thus, in DRG neurons, the TRPV1 current densities were significantly smaller in allyl isothiocyanate (AITC)-sensitive DRG neurons than in AITC-insensitive cells and spontaneous TRPA1 channel activity inhibited the TRPV1 channels via Ca 2+ elevation (Masuoka et al, 2017). Indeed 37% of H 2 S induced Ca 2+ transients were inhibited by capsazepine which indicates mainly activation of TRPV1 receptors.…”