TRPV2

Transient receptor potential cation channel subfamily V (for vanilloid) subtype 2 (TRPV2 for short, from "transient receptor potential cation channel subfamily V member 2") is a calcium-permeable cation channel expressed in sensory neurons of the vertebrate central and peripheral nervous systems. TRPV2, unlike TRPV1, is expressed in medium to large neurons of the spinal cord, brain, and motor neurons. (TRPV2 and TRPV1 share 50% sequence identity). TRPV2 was initially characterized as a noxious heat sensor, but it also has mechanosensory properties (Aguettaz E et al. 2017; Shibasaki K 2016).

TRP channels are phylogenetically early signaling pathways (they can be detected as early as yeast cells). The first TRP channel was identified in 1989 in the context of visual perception in Drosophila melanogaster. In a Drosophila mutant (trp343), it was shown that its photoreceptors responded to light stimuli only with a transient, i.e. rapidly inactivating, membrane current. In the non-mutated wild type, however, the current flow persisted as long as light hit the photoreceptor. The mutant protein -TRP- was cloned in 1989. Thus, the name "transient receptor potential" - TRP- refers to the description of a phenotype of a mutant of the fruit fly Drosophila melanogaster. TRP channels exert important functions in primary signaling pathways for the regulated influx of Ca2+ into a cell in both vertebrates and non-vertebrates. TRP channels in humans play an important role in the sensation of different types of taste (sweet, bitter, umami) as well as in the perception of pain, heat, warmth or cold, pressure and light. It is believed that some TRP channels in the body behave like microscopic thermosensors. So far, 28 TRP channel genes have been identified in mammals (Nilius B et al. 2011).

Functional analyses showed that TRPV2 does not respond to capsaicin, low pH, or moderate heat. The ion channel is activated only at temperatures above 52°C. Repeated heat stimuli sensitize the channel, as evidenced by a lower activation temperature.

TRPV2 is thought to be the molecular transmitter of lightly myelinated Aδ2 fibers. In addition, TRPV2 has been found in cervical innervating neurons and in gingival neurons. Coexpression with TRPV1 was rarely found. In nonneuronal tissues, TRPV2 likely responds to stimuli other than damaging heat.

TRPV2 apparently plays a key role in the physiological processes of the heart. The involvement of TRPV2 in stretch-dependent responses in cardiomyocytes has been described (Aguettaz E et al. 2017). TRPV2 is involved in cardiac compensatory mechanisms in response to physiological or pathological stress.TRPV2 and TRPV1 are involved in the pathogenesis of myocardial infarction. They are able to ensure cardiac tolerance to ischemia/reperfusion. Evidence suggests that TRPV2 channels are involved in the pathogenesis of dilated cardiomyopathy. Excessive expression of TRPV2 leads to chronic Ca2+ overload of cardiomyocytes, which may contribute to the development of cardiomyopathy (Gorbunov AS et al. 2019).

Furthermore, TRPV2 appears to be required for phagocytic activity of macrophages. The mechanism is as yet unclear (Fricke TC et al. 2019).

It is suggested that TRPV2 may be an important drug target due to its broad expression patterns and important physiological functions (Aguettaz E et al. 2017; Shibasaki K 2016).

1. Aguettaz E et al (2017) Stretch-activated TRPV2 channels: Role in mediating cardiopathies. Prog Biophys Mol Biol 130:273-280.
2. Fricke TC et al. (2019) Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2. Proc Natl Acad Sci U S A 116:24359-24365.
3. Gorbunov AS et al (2019) Physiological and Pathological Role of TRPV1, TRPV2 and TRPV4 Channels in Heart. Curr Cardiol Rev 15:244-251.
4. Mathar I et al (2014) Handb Exp Pharmacol 222:461-487.
5. Nilius B et al (2011) The transient receptor potential family of ion channels. Genome Biol 12:218.
6. Shibasaki K (2016) Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor. J Physiol Sc 66:359-365.