Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PL010

Keynote Lecture

TRP ion channels - Multimodal sensors and guardians of homeostasis

J. Siemens1

1. University of Heidelberg, Heidelberg, Germany.

Transient receptor potential (TRP) ion channels have been identified as versatile, multimodal molecular sensors. Particularly, several members of the extended TRP ion channel family detect temperature changes in the somatosensory nervous system. Pharmacology and genetic deletion experiments have shown that TRP channels are necessary for mediating responses to painfully hot or cold temperatures and that they become sensitized under inflammatory conditions leading to exacerbated nociceptive signals. TRPs have therefore emerged as targets for analgesic therapy. Besides constituting a warning system alerting us about noxious thermal conditions, temperature detection in the innocuous range serves another important feat: Mammalian organisms possess the remarkable ability to maintain internal body temperature (Tcore) within a narrow range close to 37°C despite wide environmental temperature variations. The brain's neural "thermostat" is made up by central circuits in the hypothalamic preoptic area (POA), which orchestrate peripheral thermoregulatory responses to maintain Tcore. How the POA detects and integrates temperature information to achieve thermal balance is largely unknown. Here, in the first part of the lecture, I will focus on the capsaicin receptor TRPV1, its function as a peripheral temperature sensor and its modulation in the context of inflammatory signals. In the 2nd part I will discuss our recent findings that implicate TRPM2, another thermo-sensitive TRP channel, in hypothalamic thermoregulation. I will conclude by presenting some preliminary results and an outlook about future experiments geared to address key questions concerning internal (deep brain) temperature detection and thermoregulation.

Where applicable, experiments conform with Society ethical requirements