VR1

VR1, originally vanilloid receptor 1, is an ion channel encoded by the TRPV1 gene and a member of the transient receptor potential (TRP) channel family. It functions as a non-selective cation channel that is preferentially expressed in nociceptive sensory neurons of dorsal root and trigeminal ganglia. VR1 is activated by heat, capsaicin, and acidic pH, and can be modulated by endogenous ligands. It plays a central role in transducing noxious thermal and chemical stimuli, contributing to the sensation of scalding heat and inflammatory pain.

Discovery and naming: VR1 was identified in the late 1990s as a receptor responsive to capsaicin, initially described as vanilloid receptor 1; later renamed TRPV1 to reflect its association with the TRP channel family.

Structure and expression: VR1 subunits form tetrameric channels with six transmembrane segments per subunit and a pore-forming loop between S5 and S6. The N-terminus contains ankyrin repeat domains; the channel is intracellularly expressed with localization in peripheral sensory terminals.

Activation and ligands: Capsaicin binds to VR1 with high affinity, opening the channel and allowing calcium and sodium influx. High temperatures above approximately 43°C and extracellular protons also activate VR1. Endogenous ligands, including endocannabinoids and vanilloids, can modulate activity.

Physiological and clinical relevance: VR1-mediated signaling contributes to inflammatory and neuropathic pain and thermosensation. VR1 antagonists have been explored as analgesics, though some clinical trials showed side effects such as impaired heat sensing or hyperthermia.