Sensing the heat with TRPM3

Abstract

Heat sensation, the ability to detect warm and noxious temperatures, is an ancient and indispensable sensory process. Noxious temperatures can have detrimental effects on the physiology and integrity of cells, and therefore, the detection of environmental hot temperatures is absolutely crucial for survival. Temperature-sensitive ion channels, which conduct ions in a highly temperaturedependent manner, have been put forward as molecular thermometers expressed at the endings of sensory neurons. In particular, several temperature-sensitive members of the transient receptor potential (TRP) superfamily of ion channels have been identified, and a multitude of in vivo studies have shown that the capsaicin-sensitive TRPV1 channel plays a key role as a noxious heat sensor. However, Trpv1-deficient mice display a residual heat sensitivity suggesting the existence of additional heat sensor(s). In this chapter, we provide evidence for the role of the non-selective calcium-permeable TRPM3 ion channel as an additional heat sensor that acts independently of TRPV1, and give an update of the modulation of this channel by various molecular mechanisms. Finally, we compare antagonists of TRPM3 to specific blockers of TRPV1 as potential analgesic drugs to treat pathological pain.

Increasing Warmth in Adolescents with Anorexia Nervosa: A Randomized Controlled Crossover Trial Examining the Efficacy of Mustard and Ginger Footbaths

“…ermal sensation is mediated by temperature-sensitive ion channels, most of which belong to the TRP ion channel superfamily. Activation of these ion channels leads to a depolarization of sensory neurons in the peripheral nervous system, whereby the signal is transmitted to the central nervous system and interpreted as a sensory response [21,22,49,50]. Of note, TRP channels can be activated not only by temperature, voltage, pressure, and osmolarity [22] but also by the binding of chemical ligands such as GI or MU [21][22][23].…”

TRPM3_miR-204: a complex locus for eye development and disease

“…Functional expression studies in transfected cells (mostly HEK293) or in cultured primary cells (e.g., β cells, neurons), coupled with electrophysiological (e.g., patch-clamp) recording and fluorometric Ca 2+ imaging techniques have been used to characterize the permeability and gating properties of the central canonical TRPM3-cation pore ('alpha-pore') in the absence or presence of known agonists including PS and/or heat [47,48,50,51,[57][58][59][60][61][62]. Two human kidneyderived TRPM3 isoforms (hTRPM3_1555 and hTRPM3_ 1325 amino-acids) were the first to be characterized as spontaneously or constitutively active Ca 2+ influx channels located in the cell membrane and were inhibited, nonspecifically, by trivalent lanthanides La 3+ and Gd 3+ [108,109].…”

“…Rather, TRPM3 channel activity in vivo has been implicated in a variety of neuronal and non-neuronal cellular processes. These include secretion of insulin by pancreatic β cells [40][41][42] and hyaluronic-acid from synovial fibroblasts [43], glutamatergic transmission of cerebellar Purkinje cells [44], oligodendrocyte maturation and CNS myelination [45], noxious heat-sensing by dorsal root ganglia (DRG) neurons [46][47][48][49][50], neuropeptide release and inflammatory pain [42], mechanosensing in vascular smooth muscle cells [51] and periodontal ligament cells during bone remodeling [52,53], and osmosensing hypotonic stress in ductus arteriosus constriction [54] and renal epithelial cells [55]. Further, TRPM3 channel activity has been shown to promote the growth of clear cell renal cell carcinoma by stimulating oncogenic (macro) autophagy dependent on microtubule-associated protein 1 light chain 3α (LC3A) and LC3B [56].…”

“…In vitro functional expression studies have determined that TRPM3 channels are activated by several structurally unrelated agonists including (1) the endogenous excitatory neurosteroid pregnenolone sulfate, which can also weakly activate TRPM1 channels [51,[57][58][59][60][61][62][63]; (2) cell-membrane phosphoinositol phosphates [64][65][66]; and (3) noxious heat [46][47][48][49][50]. Conversely, they are inhibited by (1) certain clinically approved drugs including nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., mefenamic acid), antibiotics (e.g., voriconazole, which also inhibits TRPM1 channels), sex-steroids (e.g., progesterone), and synthetic drug-like antagonists [40,41,51,61,[67][68][69][70][71][72]; (2) naturally occurring plant-derived secondary metabolites (e.g., citrus flavanones) [73][74][75]; and (3) Gprotein coupled receptor βγ subunits [76][77][78][79].…”

What is new about mild temperature sensing? A review of recent findings

“…A first physiological function of TRPM3 was described in the pancreas, where the channel is expressed in insulin-secreting β-cells and was suggested to modulate insulin release under specific conditions [72]. It was established as a heatsensitive ion channel with a temperature threshold >40°C, in sensory neurons where it is coexpressed with TRPV1 [35,73].…”