Summary: Free choline and ATP contents were mea sured in Mongolian gerbil hippocampal slices (tissue) and incubation media (media) during exposure to 30 min of aglycemia, high potassium, anoxia, or ischemia. Changes in choline levels reflected the degree of energy reduction, lower ATP levels being associated with high choline (4-fold increase during exposure to high potassium and an oxia, and II-fold increase during ischemia). Media (ex tracellular) choline was particularly affected and in creased about twofold during relatively mild energy depletion (e.g., aglycemia), but tissue choline content was less sensitive to energy reduction. A plot of choline vs. ATP levels indicated a nonlinear correlation, and the sharp increase in choline occurred when ATP values fell Choline is a precursor not only for acetylcholine, but also for phospholipids (phosphatidylcholine) and sphingomyelin in the brain. Thus, choline is involved in two important aspects of brain function: neurotransmission and the maintenance of cell membrane integrity. Both aspects are affected by a decrease in energy reserves. Synthesis and storage of acetylcholine are glucose and energy dependent (Gibson and Blass, 1976;Yamagata and Parsons, 1989) 308to about 2.5 nmollmg of protein. Inhibition of acetylcho line sterase by \0 fLM physostigmine during ischemia did not prevent an increase in choline contents but rather enhanced them, indicating that acetylcholine hydrolysis was not the source of free choline. Formation of free choline was Ca 2 + independent. These findings suggest the involvement of phospholipase D and phosphatidyl choline hydrolysis in free choline formation during energy stress. The extent of choline formation may be an indi cator of the degree of membranal damage, which in turn reflects damage to the metabolic machinery of the cell.

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