Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels

Willem J. Laursen, Eve R. Schneider, Dana K. Merriman, Sviatoslav N. Bagriantsev, Elena O. Gracheva

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


The ability to sense heat is crucial for survival. Increased heat tolerance may prove beneficial by conferring the ability to inhabit otherwise prohibitive ecological niches. This phenomenon is widespread and is found in both large and small animals. For example, ground squirrels and camels can tolerate temperatures more than 40°C better than many other mammalian species, yet a molecular mechanism subserving this ability is unclear. Transient receptor potential vanilloid 1 (TRPV1) is a polymodal ion channel involved in the detection of noxious thermal and chemical stimuli by primary afferents of the somatosensory system. Here, we show that thirteen-lined ground squirrels (Ictidomys tridecemlineatus) and Bactrian camels (Camelus ferus) express TRPV1 orthologs with dramatically reduced temperature sensitivity. The loss of sensitivity is restricted to temperature and does not affect capsaicin or acid responses, thereby maintaining a role for TRPV1 as a detector of noxious chemical cues. We show that heat sensitivity can be reengineered in both TRPV1 orthologs by a single amino acid substitution in the N-terminal ankyrin-repeat domain. Conversely, reciprocal mutations suppress heat sensitivity of rat TRPV1, supporting functional conservation of the residues. Our studies suggest that squirrels and camels co-opt a common molecular strategy to adapt to hot environments by suppressing the efficiency of TRPV1-mediated heat detection at the level of somatosensory neurons. Such adaptation is possible because of the remarkable functional flexibility of the TRPV1 molecule, which can undergo profound tuning at the minimal cost of a single amino acid change.

Original languageEnglish
Pages (from-to)11342-11347
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number40
StatePublished - Oct 4 2016

Bibliographical note

Funding Information:
We thank Jena Goodman, Owen Funk and Jon Matson for technical assistance, and members of the E.O.G. and S.N.B. laboratories for their contributions throughout the project. This study was partly funded by fellowships from the Arnold and Mabel Beckman Foundation and Rita Allen Foundation, NIH Grant 1R01NS091300-01A1 (to E.O.G.), American Heart Association Grant 14SDG17880015, National Science Foundation CAREER Award 1453167 (to S.N.B.), and by the Axle Tech International Endowed Professorship (to D.K.M.). E.R.S. was supported by NIH Training Grant T32HD007094, and W.J.L. was supported by NIH Training Grant T32HG319810.

Publisher Copyright:
© 2016, National Academy of Sciences. All rights reserved.


  • Bactrian camel
  • Sensory physiology
  • TRPV1
  • Thermosensation
  • Thirteen-lined ground squirrel

ASJC Scopus subject areas

  • General


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