Our primary interest is understanding what makes some animal species tolerant to severe hypoxia and others intolerant. Of particular interest are the underlying cellular mechanisms that effectively reduce cellular energetic demands (in terms of ATP utilization) with the onset of hypoxia. Key to surviving long term severe hypoxia is the ability to reduce cellular ATP utilization. One major site of ATP utilization for all cells is the maintenance of cellular ion gradients, the loss of gradients being one hallmark of hypoxic cell injury. Using a brain sheet and hepatocyte preparation from the western painted turtle, the most hypoxia tolerant vertebrate known, we are studying the second messenger pathways regulating hypoxic suppression of brain glutamate receptor and liver Na+ /K+ ATPase, both of which we have previously demonstrated to be actively down-regulated in hypoxia. We are also interested in the suite of proteins expressed in hypoxically preconditioned mammalian tissues. One of these (HSP 70) we have detected at the mRNA level in hypoxically stressed turtle hepatocytes. We are currently investigating the role of adenosine in the hypoxic expression of HSP 70. A better understanding of these mechanisms may lead to improved clinical interventions where hypoxia is life threatening.