"Key to surviving anoxia is the shutting off of energy-utilizing cellular activities, such as the synthesis of proteins and perhaps most importantly reducing the activity of energy intensive ion pumps," according to Leslie T. Buck, a physiologist at University of Toronto's Zoology Department. Whereas turtles and many other animals have shutoff mechanisms, humans and many mammals don't.
"However, basic biochemical pathways are common to almost all species, certainly among reptiles (turtles), fish, birds and mammals," Buck said, adding: "Therefore, the basic signals and pathways that permit anoxia-tolerance in the turtle must also be present in mammals."
In studying the natural mechanisms of anoxia tolerance, Buck's lab focused on a particular ion channel, the N-methyl-D-aspartate (NMDA) receptor. This receptor/channel is strongly associated with anoxic damage in the mammalian brain by permitting a very large flow of calcium ions into the cell during anoxia. Unlike anoxia-sensitive mammals, this doesn't occur in the western painted turtle's brain.
*Paper presentation: "NMDA receptor regulation by mitochondrial KATP channels and adenosine receptors in cortical neurons of the anoxia-tolerant western painted turtle," 12:30 p.m.-3 p.m. Sunday April 3, Physiology 381.3/board #A558. On view 7:30 a.m. - 4 p.m. Others in the research team are Damian Shin and Matthew Pamenter.
Featured topic: Buck is also participating in "Mechanisms of metabolic depression: comparative aspects," Sunday April 3, room 30 B/C beginning at 10:30 a.m. His presentation is scheduled for noon.
Buck is presenting the research at the 35th Congress of the International Union of Physiological Sciences in San Diego, March 31 - April 5, 2005.
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."
Funding. Research was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) grant.
The 35th Congress of the International Union of Physiological Sciences is in San Diego, March 31 - April 5, 2005. The Congress (http://www.iups2005.org/) is organized by the six member societies of the U.S. National Committee of the IUPS, the American Physiological Society, the Society for Neuroscience, the Microcirculatory Society, the Society of General Physiologists, the Biomedical Engineering Society, and the Society for Integrative and Comparative Biology, under the auspices of the U.S. National Academy of Sciences.
The IUPS conference, held every four years, runs concurrently this year with Experimental Biology 2005 at the San Diego Convention Center.
The American Physiological Society (APS), which is hosting IUPS, was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes nearly 4,000 articles every year in its 14 peer-reviewed journals. In May, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).
Editor's Note: For further information or to schedule an interview with a member of the research team, please contact Mayer Resnick at the IUPS/APS newsroom @ 619.525.6228 (March 31-April 6), or 301.332.4402 (cell) or 301.634.7209 (office), or Stacy Brooks at 240.432.9697 (cell) or 301.634.7253 (office).
A searchable online program for IUPS and EB is at http://www.faseb.org/meetings/eb2005/call/default.htm