BUCK, Leslie T; University of Toronto: Channel Arrest in the Anoxic Turtle Brain

It has been 16 years since the channel arrest hypothesis was introduced by Peter Hochachka (1986). His realization that ATP consuming membrane functions, primarily ion movement, must be reduced in order to survive long-term anoxia initiated a search by comparative physiologists for the sites of regulation and the mechanisms of control. The main sites appear to be ion channels and although there are many indirect demonstrations of channel arrest direct evidence has been slow in coming. In brain sheets from the anoxia-tolerant western painted turtle I have measured N-methyl-D-aspartate receptor (NMDA) single-channel and whole-cell currents during an acute normoxic/anoxic transition and found a 60% reduction in channel open time. Not only is this result reproducible with the normoxic application of adenosine, a putative low oxygen signal, but it is also prevented by the inclusion of phosphatase inhibitors and application of calcium chelators via the recording electrode. This is the first direct measure of ion channel arrest and indicates the involvement of an underlying second messenger pathway, just as predicted by the channel arrest hypothesis. Hochachka, P.W. 1986, Defense Strategies against Hypoxia and Hypothermia, Science, 231:234.