The objective of this project is to provide new information on the cellar mechanisms that explain the ability of many 'cold blooded' animals to tolerate conditions of low (or no) oxygen and low temperature. The ability of many vertebrate animals to withstand environmental conditions that are completely incompatible with human life has intrigued scientist and laymen for centuries. We now know that some fish, amphibians (i.e., frog larvae) and reptiles (turtles, for example) are capable of surviving days, weeks, or even months buried in the mud at the bottom of frozen ponds, even though there may be essentially no oxygen present at all. While some species remain in a state of hibernation, during which their metabolism virtually comes to a halt, many other animals remain fully active at body temperatures that would be quickly fatal to humans. The mechanisms by which these animals tolerate such extreme conditions are very poorly understood. The goal of this project, then, is to begin to understand the fundamental mechanisms by which animals that are in many ways similar to humans are able to function under conditions so foreign to our existence. The key to this understanding may be differences in the way that substances such as calcium and potassium are permitted to move through the walls of cells in crucial organs, such as the brain and heart. If so, it may ultimately be possible to identify drugs that would expand the resistance of humans to extreme environmental conditions.