Oxygen sensitive synaptic neurotransmission in anoxia-tolerant turtle cerebrocortex.
Anoxia rapidly elicits hyper-excitability and cell death in mammal brain but this is not so in anoxia-tolerant turtle brain where spontaneous electrical activity is suppressed by anoxia (i.e. spike arrest; SA). In anoxic turtle brain extracellular GABA concentrations increase dramatically and impact GABAergic synaptic transmission in a way that results in SA. Here we briefly review what is known about the regulation of glutamatergic signalling during anoxia and investigate the possibility that in anoxic turtle cortical neurons GABA(A/B) receptors play an important role in neuroprotection. Both AMPA and NMDA receptor currents decrease by about 50% in anoxic turtle cerebrocortex and therefore exhibit channel arrest, whereas GABA-A receptor currents increase twofold and increase whole-cell conductance. The increased post synaptic GABA-A receptor current is contrary to the channel arrest hypothesis but it does serve an important function. The reversal potential of the GABA-A receptor (E(GABA)) is only slightly depolarized relative to the resting membrane potential of the neuron and not sufficient to elicit an action potential. Therefore, when GABA-A receptors are activated, membrane potential moves to E(GABA) and prevents further depolarization by glutamatergic inputs during anoxia by a process termed shunting inhibition. Furthermore we discuss the presynaptic role of GABA-B receptors and show that increased endogenous GABA release during anoxia mediates SA by activating both GABA-A and B receptors and that this represents a natural oxygen-sensitive adaptive mechanism to protect brain from anoxic injury.
Department of Cell and Systems Biology, University of Toronto, Toronto, Canada. les.buck@utoronto.ca
Leslie T
LT
Buck
D W R
DW
Hogg
C
C
Rodgers-Garlick
M E
ME
Pamenter
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014426:Turtles / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D010100:Oxygen