Glial Hsp70 Protects K+ Homeostasis in the Drosophila Brain during Repetitive Anoxic Depolarization

Neural tissue is particularly vulnerable to metabolic stress and loss of ion homeostasis. Repetitive stress generally leads to
more permanent dysfunction but the mechanisms underlying this progression are poorly understood. We investigated the
effects of energetic compromise in Drosophila by targeting the Na+/K+-ATPase. Acute ouabain treatment of intact flies
resulted in subsequent repetitive comas that led to death and were associated with transient loss of K+ homeostasis in the
brain. Heat shock pre-conditioned flies were resistant to ouabain treatment. To control the timing of repeated loss of ion
homeostasis we subjected flies to repetitive anoxia while recording extracellular [K+] in the brain. We show that targeted
expression of the chaperone protein Hsp70 in glial cells delays a permanent loss of ion homeostasis associated with
repetitive anoxic stress and suggest that this is a useful model for investigating molecular mechanisms of neuroprotection.