Our understanding of how the mammalian somatosensory system detects noxious cold is still limited. While the role of TRPM8 in signaling mild non-noxious coolness is reasonably understood, the molecular identity of channels transducing painful cold stimuli remains unresolved. TRPC5 was originally described to contribute to moderate cold responses of dorsal root ganglia neurons in vitro, but mice lacking TRPC5 exhibited no change in behavioral responses to cold temperature. The question of why a channel endowed with the ability to be activated by cooling contributes to the cold response only under certain conditions is currently being intensively studied. It seems increasingly likely that the physiological detection of cold temperatures involves multiple different channels and mechanisms that modulate the threshold and intensity of perception. In this review, we aim to outline how TRPC5 may contribute to these mechanisms and what molecular features are important for its role as a cold sensor.

• Keywords
• Cold sensation, Orai1, Stromal interaction molecule 1, Thermo-TRP channel, Transient receptor potential canonical, Voltage-dependent gating,
• MeSH
• TRPC Cation Channels * metabolism   MeSH
• TRPM Cation Channels metabolism   MeSH
• Humans MeSH
• Mice MeSH
• Cold Temperature * MeSH
• Ganglia, Spinal metabolism   physiology   MeSH
• Thermosensing * physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• TRPC Cation Channels * MeSH
• TRPM Cation Channels MeSH
• TRPC5 protein, human MeSH Browser
• Trpc5 protein, mouse MeSH Browser