Low cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels
Significance Thirteen lined ground squirrels and Bactrian camels are capable of withstanding elevated environmental temperatures. In mammals, the polymodal transient receptor potential vanilloid 1 (TRPV1) ion channel responds to temperatures >40 degC and marks peripheral neurons responsible for detecting noxious heat. However, we find that both squirrels and camels express TRPV1 channels with dramatic decreases in thermosensitivity in the physiologically relevant range. To regain heat sensitivity, squirrel and camel TRPV1 require substitution of a single conserved amino acid. These data point to a common molecular mechanism used by camels and squirrels to adapt to high temperatures and reveal a remarkable functional plasticity of temperature activation of the TRPV1 channel. 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 degC 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.
Proceedings of the National Academy of Sciences