Naturally evolved cellular adaptations to anoxia

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The Buck lab is investigating the cellular mechanisms that permit some vertebrate species, such as freshwater turtles, goldfish and snails to survive without oxygen (anoxia) for days to months during winter. We use both a liver and brain cell model to study the mechanisms of anoxia tolerance. Key to surviving anoxia is the shutting off of energy utilizing cellular activities, such as the synthesis of new proteins and maintaining ion gradients across cell membranes. We have previously shown that protein synthesis decreases by about 90%, the pump that maintains ion gradients decreases by 75%, and ion channel activity (pathways for ions to cross membranes) decreases and in one case increases. The ability to reduce the rate of these energy consuming reactions is something that mammals (humans) lack. However, basic biochemical pathways are common to almost all species, certainly amongst reptiles (turtles), fish, birds and mammals. Our goal is to determine the natural cellular pathways responsible for shutting off energy consuming processes in anoxia-tolerant species. We have already identified several possible pathways and discovered that brain excitatory signaling involving glutamate is decreased, while inhibitory activity involving GABA is increased during anoxic periods. These results are remarkably similar to the way in which volatile anesthetics reduce brain activity in humans and we may have uncovered a natural anesthetic mechanism. Brain is an electrically excitable tissue and we are also investigating anoxic regulation of ion channels in non-excitable tissue - liver. In the next grant cycle we will continue to explore the electrophysiological properties and second messenger pathways of brain and liver tissue to better understand which ion channels are regulated in a way that reduces energetic demands and permits anoxic survival.