New potassium channel blockage short-circuits turtle's shutoff mechanism

A known protective factor is adenosine, a compound that accumulates in both mammalian and reptile (turtle) brains in response to low oxygen levels. It reduces the inflow of calcium through NMDA receptors during anoxia and is associated with brain protection. "However, our work suggests that adenosine isn't the only protective factor. Even with the adenosine pathways inhibited, calcium influx in anoxic turtle brain still decreases," Buck noted.

Mathew Pamenter, a graduate student in the lab, had the idea to investigate a relatively newly discovered potassium channel (mitochondrial KATP channel) as a possible regulator of NMDA receptor activity during anoxia. "When this new channel was inhibited, the protective decrease in calcium influx previously observed in anoxic turtle brain didn't occur," Buck said. "This result indicates that this channel plays a key role in the natural anoxia-tolerance of the turtle and opens a new research direction in this area."

Next steps. Buck said one avenue of investigation is to see whether the potassium channels may be part of an oxygen sensing mechanism, which some believe. "Our ultimate goal is to determine the natural cellular pathways responsible for oxygen sensing and the shutting off of energy consuming processes in the turtle," Buck said. "Then I want to apply this knowledge to human clinical situations, such as improving outcomes of cerebral stroke and cardiac infarct, and the development of better anesthetics."

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3-Apr-2005