Aims: 

Of the four heat-activated ion channels from the vanilloid-type TRP group (TRPV1-4), the least is known about TRPV2. Expressed in a variety of neuronal and non-neuronal tissues, TRPV2 is a high threshold (>52°C) heat receptor channel, blocked by ruthenium red and activated by 2-aminoethoxydiphenyl borate, and proposed to act as a sensor for intense noxious heat in mammalian sensory neurones. Our aim was to characterize TRPV2 in heterologous expression systems in terms of pharmacology and temperature dependence and to provide new evidence for functional expression of TRPV2 in rat DRG neurones in primary culture.

Methods: 

Rat TRPV2 was transiently transfected into HEK293t cells and its activation by heat was investigated using the patch-clamp technique. The same method was used to record heat-activated currents in capsaicin-sensitive and capsaicin-insensitive DRG neurones from the rat.

Results: 

In this study we propose a new pharmacological tool to distinguish between the heat responses of TRPV2 and the closely related channel TRPV1: the trivalent cations lanthanum and gadolinium had opposite effects on the two channels, blocking TRPV2 and sensitising TRPV1 to heat. Recordings from rat dorsal root ganglion cultures revealed that medium and large capsaicin-insensitive neurones express a heat-activated current that closely matches the temperature dependence, self-sensitisation and pharmacological properties of TRPV2 in a heterologous expression system.

Conclusion: 

Taken together our results provide new evidence for a role of TRPV2 in mediating high-threshold heat responses in a subpopulation of mammalian sensory neurones.