Paralytic hypo-energetic state facilitates anoxia tolerance despite ionic imbalance in adultDrosophila melanogaster

Abstract

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.

Effects of anoxia on ATP, water, ion and pH balance in an insect (Locusta migratoria)

“…ATP concentrations tend to decrease even further with prolonged anoxia as has been shown in L. migratoria (Weyel and Wegener, 1996) and D. melanogaster (Campbell et al, 2018). It has been suggested that anoxic mortality only occurs when ATP levels are close to zero and anoxic survival may therefore involve some ability to regulate/maintain ATP at a low but non-zero level (Campbell et al, 2018). The low ATP levels are likely to reduce the activity of ion-motive ATPases, resulting in a gradual loss of ion homeostasis during anoxia.…”

“…fruitfly larvae; see Callier et al, 2015), enter a neuromuscular coma when exposed to anoxia (Wegener, 1993;Rodgers et al, 2010) and longer anoxic exposures reduce survival and increase the time it takes for insects to recover from anoxia (Wu et al, 2002;Lighton and Schilman, 2007). The lack of aerobic ATP production disrupts ATP homeostasis, causing ATP concentrations to drop rapidly (Wegener, 1993;Hoback, 2012;Campbell et al, 2018). ATP concentrations tend to decrease even further with prolonged anoxia as has been shown in L. migratoria (Weyel and Wegener, 1996) and D. melanogaster (Campbell et al, 2018).…”

“…The lack of aerobic ATP production disrupts ATP homeostasis, causing ATP concentrations to drop rapidly (Wegener, 1993;Hoback, 2012;Campbell et al, 2018). ATP concentrations tend to decrease even further with prolonged anoxia as has been shown in L. migratoria (Weyel and Wegener, 1996) and D. melanogaster (Campbell et al, 2018). It has been suggested that anoxic mortality only occurs when ATP levels are close to zero and anoxic survival may therefore involve some ability to regulate/maintain ATP at a low but non-zero level (Campbell et al, 2018).…”

“…This is particularly problematic if extracellular K + concentration rises (Rodgers et al, 2010;Campbell et al, 2018), as a disrupted transmembrane [K + ] gradient leads to cell membrane depolarization, which can initiate apoptotic or necrotic processes (Hochachka, 1986;Bortner et al, 2001;Armstrong et al, 2011;Bayley et al, 2018). Elevated extracellular [K + ] has been observed in both brain (Armstrong et al, 2011;Rodriguez and Robertson, 2012) and hemolymph (Campbell et al, 2018) of anoxic D. melanogaster. Further, it is likely that the continued reliance on anaerobic metabolism causes severe acidification as has been demonstrated in the hemolymph of D. melanogaster (Campbell et al, 2018).…”

An impressive capacity for cold tolerance plasticity protects against ionoregulatory collapse in the disease vector,Aedes aegypti

“…Mosquito larvae obtain gaseous oxygen from the water surface through a siphon on the posterior end of their abdomen, so sinking during cold stress may limit access to oxygen during a cold stress and cause systemic hypoxia. Like cold stress, anoxia has been demonstrated to cause disruptions of ion homeostasis leading to hyperkalemia in Drosophila (Campbell, Andersen, Overgaard, & Harrison, 2018), meaning an inability to access sufficient oxygen during chill coma may further contribute to ionic imbalance and injury in the cold in this aquatic insect. Alternatively, as the metabolic rate of ectotherms is strongly supressed during cold exposure, larvae may obtain sufficient oxygen from the surrounding water during cold stress to fuel metabolism and avoid the downstream consequences of hypoxia.…”