The TRP superfamily is a functionally diverse group of cation channels with widely diverging functional properties. First, there is a striking diversity in the pore permeability of TRP channels, ranging from non-selective cation permeability to high selectivity for divalent cations . Moreover, there is a daunting variety of stimuli that can regulate the gating of the TRP channels, such as physical stimuli (temperature, voltage, mechanical stress), exogenous ligands, intracellular cations and lipid components of the plasma membrane . Several TRP channels, including TRPV1, TRPV4, TRPM3, TRPM8 and TRPA1, are implicated in somatosensation, acting as integral molecular components of the sensory machinery involved in chemo, thermo and/or mechanosensation . Based on experimental data, there was ample evidence for the expression of other TRP channels in sensory neurons, which may either operate as sensors of as yet undefined stimuli or exert other (housekeeping) functions in these cells. The present study had two main aims: (1) to provide a systematic analysis of all TRP channels in different sensory ganglia in mice; and (2) to detect possible ganglion-to-ganglion variations in TRP channel expression. Although destinations of every single DRG neuron projections in mice are still unclear, a homology to human DRG neurons might be instrumental to anticipate TRP channel functions in target organs . In humans, the cervical DRGs mainly projects to dermatomes of the head, upper limbs, hands as well as the eye. The thoracic DRGs innervate dermatomes of the chest and the abdomen (T1-T5 supply the stomach, liver, gallbladder and pancreas while T10-T12 account for the kidneys). The lumbar DRGs innervate dermatomes of the inguinal regions, the anterior and inner surfaces of the lower limbs and feet, while the sacral DRGs project to the remaining posterior and outer surfaces of the lower limbs and lateral margin of the feet (L1-L3 innervate the intestines, L4-S2 are responsible for the innervations of the bladder and prostate, while S3-S5 innervate external genitalia).
We were able to confirm expression of TRP channels that have been previously proposed as sensors in TG and DGR neurons, including TRPA1, TRPV1, TRPV2, TRPV4, TRPM3 and TRPM8 [9, 18–22]. Notably, we found that expression levels of TRPV1 and TRPM8 showed statistically significant variation between anatomically different ganglia. For example, TRPM8 expression was significantly lower in the DRG from thoracic segments compared to TG or other regions of the spinal cord, whereas TRPV1 showed significantly higher expression levels in L6 and S1 segments. Such variations may contribute to the variability in functional TRPM8- or TRPV1-mediated responses in neurons isolated from different segments.
Amongst the most highly expressed genes there were also a number of TRP channels for which a function in the sensory system is not yet well established (TRPC3, TRPM7, TRPML1 and TRPP2). TRPC3, together with TRPC6, has recently been proposed as a component of a mechanotransduction complex in sensory neurons , although there is little evidence that TRPC3 on its own can form a mechano-gated channel. TRPM7 is a ubiquitously expressed channel that has been implicated in cell proliferation, organ development and intracellular Mg2+ homeostasis, although a role in mechanosensation has been suggested in some studies [24, 25]. TRPML1 is mainly found in endosomes, and may play a housekeeping role in endosome homeostasis . The function of TRPP2, a TRP channel involved in development of polycystic kidney disease , which was found to be the most highly expressed TRP channel gene in the majority of sensory ganglia, is fully unclear.
Expression of 11 TRP channels, TRPC2, TRPC6, TRPC7, TRPM1, TRPML2, TRPML3, TRPP3, TRPP5, TRPV3, TRPV5 and TRPV6, was generally low to undetectable, suggesting that these channels have no specific function in sensory neurons, or only in a very small subset of these cells.
Although these qPCR data provide a valuable comparison of expression at the mRNA level, it is important to remember that mRNA levels not always correlate with the relative abundance of these channels at the protein level or in their functional . Consequently, high mRNA levels do not always indicate that these TRP channels are functionally important, and, vice versa, low mRNA expression levels do not exclude the possibility that these TRP channels are relevant in physiology. Thus, systematic studies using TRP subtype-selective antisera could be useful to extend future studies to the protein level that will further help to assess the role of these channels at the functional level.