The Transient Receptor Potential Vanilloid Type 1 Ion Channel in Hypometabolic Response to Hypoxia

When challenged with low levels of available oxygen (hypoxia), larger mammals, including humans, attempt to maintain a consistent oxygen supply by increasing their rate of respiration. Smaller rodents and newborn mammals, on the other hand, respond to hypoxia by curtailing oxygen consumption. This latter process (hypoxic hypometabolism) involves actively regulated reductions in both metabolic rate and body temperature (3; 4; 9). Despite more than 50 years of investigation, the molecular mechanisms of this intriguing process are still unclear. Recently, the transient receptor potential vanilloid type 1 (TRPV1) receptor (best known for its response to capsaicin) has been implicated in the regulation of body temperature (5). Evidence includes the ability of TRPV1 receptor agonists and antagonists to lower and raise body temperature respectively (6; 7), as well as a demonstrated site of action within thehypothalamus (the area of the brain responsible for the regulation of body temperature) (1; 2). Based on the parallel but separately identified roles of hypoxia and TRPV1 in controlling body temperature, we reasoned that the TRPV1 ion channel may be implicated in hypoxia-induced alterations in body temperature. This present study investigates the potential involvement of the TRPV1 ion channel in hypoxia mediated hypothermia by comparing the hypoxic responses of wild-type mice and transgenetic knockout animals lacking a functional TRPV1 gene. We hypothesize that the TRPV1 knockout animals will show a blunted hypothermic response to hypoxic challenge.