Molecular basis of reversible hypothermia in mammalian hibernators
Detection and avoidance of potentially damaging temperatures is crucial for survival. At the same time, certain mammals, including desert-dwelling camels and diurnal sciurid rodents, have evolved the ability to withstand temperature extremes and are thus able to live in environments otherwise inhospitable to many species. Here, using thirteen-lined ground squirrels (Ictidomys tridecemlineatus) as a laboratory model, we sought to explore the molecular basis for heat tolerance at the level of the somatosensory system. In mammals, noxious heat is detected by a specific subpopulation of primary afferent neurons that express TRPV1, a polymodal ion channel that is activated by a variety of noxious stimuli including temperatures above ~42°C, capsaicin from chili peppers, as well as protons. However, for squirrels, our behavioral experiments and live-cell ratiometric calcium imaging of dissociated primary afferent neurons revealed significant decreases in temperature sensitivity of the channel. Furthermore, electrophysiological recordings from squirrel TRPV1 in heterologous systems demonstrated a dramatic modality-specific decrease in response to heat, thus providing a potential molecular mechanism for decreased thermosensitivity of the animals. Interestingly, we observed a similar phenomenon when we examined the TRPV1 orthologue from the famously heat-tolerant wild Bactrian camel (Camelus ferus). Thermosensitivity of both squirrel and camel TRPV1 could be fully regained via substitution of a single conserved amino acid residue in the N-terminal ankyrin repeat domain—highlighting remarkable plasticity of the TRPV1 thermosensing function. Together, our data suggest that, in order to cope with elevated temperatures, camels and squirrels both target the temperature-sensitivity of TRPV1—a channel particularly amendable to evolutionary adaptations due to its apparent low-cost functional plasticity.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.