Glial voltage-gated K+ channels modulate the neural abiotic stress tolerance of Drosophila melanogaster

Abstract

Severe abiotic stress causes insects to lose nervous function and enter a state of paralytic coma. Central to this loss of function is a spreading depolarization (SD), where a characteristic collapse of ion gradients depolarizes neuronal and glial membranes and rapidly shuts down the CNS. Despite representing a critical limit to CNS function, the stress threshold that elicits SD can be altered by the process of acclimation, though the mechanisms underlying this response remain largely unknown. Here, we made electrophysiological measurements of SD and investigated the role of K+ channels in acclimation of the CNS stress response of Drosophila melanogaster. First, we demonstrate that improved cold tolerance in the CNS elicited by cold acclimation was abolished by pharmacological blockade of K+ channels with voltage-gated K+ channels representing most of this effect. Next, we used the UAS/Gal4 model system to screen for candidate genes encoding glial voltage-gated K+ channels and found that knockdown of sei- and Shaw-encoded channels mimicked the effect of K+ blockade in cold-acclimated flies. Furthermore we show that the knockdown of glial sei-encoded channels also impair tolerance to anoxia and heat stress. These findings suggest that voltage-gated K+ channels, especially those encoded by sei, are integral to the CNS stress- and acclimation-response and we posit that this is elicited through mechanisms involving glial spatial buffering and barrier function. Establishing such causal links between tissue-specific expression of candidate genes and SD mechanisms will inevitably aid our understanding of insect ecophysiology and SD-related neuropathologies. New and NoteworthyUsing thermal acclimation and pharmacology, we demonstrate that voltage-gated K+ channels are involved in setting the threshold for cold-induced spreading depolarization (SD) in the Drosophila melanogaster CNS. Glial knockdown of channels encoded by sei and Shaw reduced the resistance to cold-induced SD, highlighting their importance in acclimation of the CNS. Glia-specific sei-knockdown also reduced tolerance to anoxia and heat. We posit that sei-channels are involved the CNS stress- and acclimation-responses through glial spatial buffering mechanisms.