K+ homeostasis and central pattern generation in the metathoracic ganglion of the locust

Rodgers, Corinne I.; LaBrie, John D.; Robertson, R. Meldrum

doi:10.1016/j.jinsphys.2009.03.004

Cited by 26 publications

(29 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We attributed the occurrence of these comas to concurrent [K + ] o surges resulting from compromised Na + /K + -ATPase activity. Previous work by our lab has documented the occurrence of this phenomenon in the migratory locust ( L. migratoria ) CNS during exposure to ouabain [21], [22], [39] and we have proposed a model for its occurrence [22], [23]. We believe that the spontaneous and repetitive surges in [K + ] o occurring in the fly brain are the essential distinguishing features of PIDs and sought to investigate exclusively the deleterious effect of repetitive anoxia in the fly brain.…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2011

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 97%

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

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fruit flies that have lower PKG expression due to genetic variation or by modulating activity through pharmacological treatment show prolonged activity in response to acute anoxia [87]. Similarly, when PKG is pharmacologically inhibited by PKG pathway blockers, the locust nervous systems exposed to acute anoxia exhibit neural protection through extended function and a delay in the increase in extracellular K + ; modulating ion channels in this fashion strengthens the membrane’s ability to maintain homeostasis [102,110]. This ‘ionic fortification’ via K + channel conductance inhibition is of importance since it is now possible to mimic the K + channel conductance dynamics of a heat shocked animal (upregulated HSPs) via an acute pharmacological treatment in only seconds, whereas natural induction after HS takes hours [105,109].…”

Section: Manipulation Of the Pkg Pathway Alters Anoxia Tolerancementioning

confidence: 99%

Alleviating Brain Stress: What Alternative Animal Models Have Revealed About Therapeutic Targets For Hypoxia and Anoxia

Milton

2013

Future Neurol.

View full text Add to dashboard Cite

While the mammalian brain is highly dependent on oxygen, and can withstand only a few minutes without air, there are both vertebrate and invertebrate examples of anoxia tolerance. One example is the freshwater turtle, which can withstand days without oxygen, thus providing a vertebrate model with which to examine the physiology of anoxia tolerance without the pathology seen in mammalian ischemia/reperfusion studies. Insect models such as Drosophila melanogaster have additional advantages, such as short lifespans, low cost and well-described genetics. These models of anoxia tolerance share two common themes that enable survival without oxygen: entrance into a state of deep hypometabolism, and the suppression of cellular injury during anoxia and upon restoration of oxygen. The study of such models of anoxia tolerance, adapted through millions of years of evolution, may thus suggest protective pathways that could serve as therapeutic targets for diseases characterized by oxygen deprivation and ischemic/reperfusion injuries.

show abstract

“…Similar increases in [K ϩ ] o are induced by hyperthermia and by disrupting mitochondrial function. Moreover, manipulation of ionic gradients, either by direct injection of high K ϩ saline into the extracellular space or by reducing Na ϩ /K ϩ ATPase activity with ouabain, generates waves of increased [K ϩ ] o that propagate throughout the neuropile and are associated with transient depression of motor pattern activity (Rodgers et al, 2007(Rodgers et al, , 2009. These phenomena share all the major characteristics of CSD, although the extent of neuronal depolarization during the locust SD-like event is unknown.…”

Section: Introductionmentioning

confidence: 99%

Suppression of Spreading Depression-Like Events in Locusts by Inhibition of the NO/cGMP/PKG Pathway

Armstrong¹,

Rodgers²,

Money³

et al. 2009

Journal of Neuroscience

View full text Add to dashboard Cite

Despite considerable research attention focused on mechanisms underlying neural spreading depression (SD), because of its association with important human CNS pathologies, such as stroke and migraine, little attention has been given to explaining its occurrence and regulation in invertebrates. In the locust metathoracic ganglion (MTG), an SD-like event occurs during heat and anoxia stress, which results in cessation of neuronal output for the duration of the applied stress. SD-like events were characterized by an abrupt rise in extracellular potassium ion concentration ([K ϩ ] o ) from a baseline concentration of ϳ8 to Ͼ30 mM, which returned to near baseline concentrations after removal of the applied stress. After return to baseline [K ϩ ] o , neuronal output (ventilatory motor pattern activity) from the MTG recovered. Unlike mammalian neurons, which depolarize almost completely during SD, locust neurons only partially depolarized. SD-like events in the locust CNS were suppressed by pharmacological inhibition of the nitric oxide/cyclic guanosine monophosphate/protein kinase G (NO/cGMP/PKG) pathway and were exacerbated by its activation. Also, environmental stressors such as heat and anoxia increased production of nitric oxide in the locust CNS. Finally, for the intact animal, manipulation of the pathway affected the speed of recovery from suffocation by immersion under water. We propose that SD-like events in locusts provide an adaptive mechanism for surviving extreme environmental conditions. The highly conserved nature of the NO/cGMP/PKG signaling pathway suggests that it may be involved in modulating SD in other organisms, including mammals.

show abstract

K+ homeostasis and central pattern generation in the metathoracic ganglion of the locust

Cited by 26 publications

References 35 publications

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

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

Alleviating Brain Stress: What Alternative Animal Models Have Revealed About Therapeutic Targets For Hypoxia and Anoxia

Suppression of Spreading Depression-Like Events in Locusts by Inhibition of the NO/cGMP/PKG Pathway

Contact Info

Product

Resources

About