Functional characterization of thermosensitive TRPV channels from holocephalan elephant shark (Callorhinchus milii) illuminate the ancestral thermosensory system in vertebrates.

Abstract

Homeostasis and survival of various animal species have been affected by changes in environmental temperature, causing animals to evolve physiological systems for sensing ambient and body temperature. Temperature-sensitive transient receptor potential (TRP) channels have multimodal properties that are activated by physical stimuli such as temperature, as well as by various chemical substances. Our goal is to understand the diversity of the vertebrate thermosensory system by characterizing the temperature-sensitive TRPV channels of the elephant shark, which belongs to the Holocephali of the cartilaginous fishes. Since elephant sharks are basal jawed vertebrates, analysis of elephant shark TRPs is critical to understanding the evolution of thermosensory systems in vertebrate lineages. We found that temperature stimulation activated elephant shark TRPVs in an electrophysiological analysis similarly to the mammalian ortholog. The thermal activation threshold of elephant shark TRPV1 (31°C) was similar to the thresholds reported for several other fish species, but was much lower than that of mammalian orthologs. Strikingly, the elephant shark TRPV4 was a cooling-activated channel with a threshold of 20°C, whereas, in several tetrapods, it is activated by warmth. These results suggest that the temperature sensitivity of TRPV4 has changed in vertebrate evolutionary lineages. Furthermore, we also found the elephant shark possesses heat-evoked TRPV3 with a threshold of 42°C, which is absent in more derived teleost fishes. Taken together, our findings elucidate that the vertebrate-type thermosensory system has already emerged in the common ancestor of jawed vertebrates, although their temperature-sensing ranges were different from those of mammals.