Paralytic hypo-energetic state facilitates anoxia tolerance despite ionic imbalance in adult .

Oxygen limitation plays a key role in many pathologies; yet, we still lack a fundamental understanding of the mechanisms responsible for variation in anoxia tolerance. Most vertebrate studies suggest that anoxia tolerance involves the ability to maintain cellular ATP despite the loss of aerobic metabolism. However, insects such as adult are able to survive long periods of anoxia (LT: ∼8 h) in a hypo-energetic state characterized by low [ATP]. In this study, we tested for possible mechanisms that allow adults to survive long periods of anoxia. Adults are paralyzed within 30 s, and after 2 h of anoxia, ATP was 3% of normal, extracellular potassium concentration ([K]) increased threefold, pH dropped 1 unit, yet survival was 100%. With 0.5-6 h of anoxia, adults maintained low but constant ATP levels while [K] and pH continued to change. When returned to normoxia, adults restored [K] and activity. With longer durations of anoxia, ATP levels decreased and [K] rose further, and both correlated tightly with decreased survival. This response contrasts with the anoxia-sensitive larval stage (LT: ∼1 h). During anoxia, larvae attempted escape for up to 30 min and after 2 h of anoxia, ATP was <1% of resting, [K] increased by 50%, hemolymph pH fell by 1 unit, and survival was zero. The superior anoxia tolerance of adult appears to be due to the capacity to maintain a paralytic hypometabolic state with low but non-zero ATP levels, and to be able to tolerate extreme extracellular ionic variability.