Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8318777 | Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology | 2018 | 10 Pages |
Abstract
The ion channel arrest hypothesis has been the foundation of three decades of research into the underlying mechanisms of hypoxia/anoxia tolerance in several key species, including: painted turtles, goldfish, crucian carp, naked mole rats, and arctic and ground squirrels. The hypothesis originally stated that hypoxia/anoxia tolerant species ought to have fewer ion channels per area membrane and/or mechanisms to regulate the conductance of ion channels. Today we can add to this and include mechanisms to remove channels from membranes and the expression of low conductance isoforms. Furthermore, possible oxygen sensing mechanisms in brain include a link to mitochondrial function, changes in the concentration of intracellular Ca2+ and reactive oxygen species, and activation of protein kinase C and a phosphatase. Importantly ion channel arrest leads to a decrease in metabolic rate that is fundamental to survival without oxygen and in brain is reflected in decreased action potential frequency or spike arrest. This results not only from a decrease in excitatory glutamatergic receptor currents but also by an increase in inhibitory GABAergic receptor currents. The surprising finding that ionic conductance through some ion channels increases is novel and contrary to the ion channel arrest hypothesis. The major insight that this offers is that key regulatory events are occurring at the level of the synapse and we therefore propose the “synaptic arrest hypothesis”.
Keywords
PKCexcitotoxic cell deathMitochondrial ATP-sensitive potassium channelECDAMPAα-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acidmKATPMPTPOGDFCCPNMDAN-methyl-d-aspartatemitochondrial outer membrane permeabilization[Ca2+]γ-amino-butyric acidAdenosine TriphosphateATPNeurotransmissionmitochondrial permeability transition poreSquirrelCalcium concentrationTurtleMOMPGoldfishOxygen glucose deprivationnaked mole rataction potentialMembrane potentialProtein kinase CCarbonyl cyanide-4-(trifluoromethoxy)phenylhydrazoneAnoxiaGABA
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Authors
Leslie T. Buck, Matthew E. Pamenter,