Examining gap junctions, NMDA and AMPA receptors for evidence of channel arrest in cortical neurons of the anoxia-tolerant turtle,  Chrysemys picta bellii.
Published: 2005
Language: eng
Number of pages: 178
Description: Unlike most vertebrates the western painted turtle (Chrysemys picta bellii) is anoxia tolerant and can survive without oxygen for weeks to months. A postulated mechanism employed in the anoxic turtle brain is a decrease in energy demanding processes for maintaining ATP levels necessary for cell function and viability. Decreasing ion channel permeability and ion flux across the plasma membrane, a phenomenon known as "channel arrest", is a key strategy leading to decreased ATP utilization and for anoxic survival in the turtle brain. The main goal of my thesis is to examine gap junctions, NMDA and AMPA receptors for evidence of channel arrest and to elucidate second messenger pathways underlying their anoxic regulation. Using both fluorescent imaging and electrophysiological techniques it was established that gap junctions do not undergo channel arrest and have a very low permeability; possibly an adaptive trait to prevent propagation of cell injury. To examine anoxic regulation of NMDA and AMPA receptor activity, an initial study was conducted to determine if pharmacological anoxia, induced by NaCN application, was a good mimic for physiological anoxia. I concluded that it was not a good mimic and all subsequent anoxic experiments were conducted using N2 gassed saline. Anoxia induced a 64% decrease in whole-cell NMDAR activity and was mediated by Ca 2+, calmodulin, and protein phosphatases 1 and 2A. The role of adenosine and KATP channels in anoxia-mediated regulation of NMDAR activity was also examined. Normoxic adenosine, via the A1 receptor, and KATP channel activation decreased NMDAR activity similar to that observed during anoxia. Yet, only KATP channels were involved in the anoxia-mediated decrease in NMDAR activity. In addition, my data suggests that KATP channel involvement may be of mitochondrial origin. When AMPAR activity was examined during anoxia, the receptor did not undergo an anoxia-mediated decrease in whole-cell currents. In conclusion, unlike gap junctions and AMPARs, NMDARs undergo channel arrest in anoxic turtle cortical neurons.
Notes: Thesis (Ph.D.)--University of Toronto, 2005.

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Source: Dissertation Abstracts International, Volume: 66-06, Section: B, page: 3002.