Expression and Function of Transient Receptor Potential Ankyrin 1 Ion Channels in the Caudal Nucleus of the Solitary Tract

Abstract

The nucleus of the solitary tract (NTS) receives visceral information via the solitary tract (ST) that comprises the sensory components of the cranial nerves VII, IX and X. The Transient Receptor Potential Ankyrin 1 (TRPA1) ion channels are non-selective cation channels that are expressed primarily in pain-related sensory neurons and nerve fibers. Thus, TRPA1 expressed in the primary sensory afferents may modulate the function of second order NTS neurons. This hypothesis was tested and confirmed in the present study using acute brainstem slices and caudal NTS neurons by RT-PCR, immunostaining and patch-clamp electrophysiology. The expression of TRPA1 was detected in presynaptic locations, but not the somata of caudal NTS neurons that did not express TRPA1 mRNA or proteins. Moreover, caudal NTS neurons did not show somatodendritic responsiveness to TRPA1 agonists, while TRPA1 immunostaining was detected only in the afferent fibers. Electrophysiological recordings detected activation of presynaptic TRPA1 in glutamatergic terminals synapsing on caudal NTS neurons evidenced by the enhanced glutamatergic synaptic neurotransmission in the presence of TRPA1 agonists. The requirement of TRPA1 for modulation of spontaneous synaptic activity was confirmed using TRPA1 knockout mice where TRPA1 agonists failed to alter synaptic efficacy. Thus, this study provides the first evidence of the TRPA1-dependent modulation of the primary afferent inputs to the caudal NTS. These results suggest that the second order caudal NTS neurons act as a TRPA1-dependent interface for visceral noxious-innocuous integration at the level of the caudal brainstem.

TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids

“…Cannabinoids have been shown to exert powerful hypotensive effects [ 83 ]. TRPV1 channels are also expressed in the central nerve terminals of sensory neurons, where peripheral afferents form synapses at the spinal dorsal horn, vagal nerve afferents at the NTS, and trigeminal nerve afferents at the caudal trigeminal nucleus [ 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. TRPV1 channels are expressed in specific locations in the higher centers of the brain, such as the descending pain pathway involving the rostral ventral medulla (RVM) and the periaqueductal gray (PAG) [ 91 , 92 , 93 , 94 , 95 , 96 ].…”

Computational Drug Repurposing Algorithm Targeting TRPA1 Calcium Channel as a Potential Therapeutic Solution for Multiple Sclerosis

“…TRPA1 is a nonselective cation channel with high permeability for Ca 2+ , which either potentiates or inactivates the chemically activated receptor [15]. TRPA1 is expressed in several tissues, such as dorsal root ganglia, rodent cortex, caudal nucleus, urinary bladder, colon innervations, and pancreatic beta cells [16,17,18,19,20,21]. Furthermore, TRPA1 is present in rodent hippocampal astrocytes, contributing to basal calcium levels regulation, inhibitory synapse efficacy, and long-term potentiation [22,23].…”