Systemic hypoxia and the depression of synaptic transmission in rat hippocampus after carotid artery occlusion.
The relationship between step reductions in inspired oxygen and the amplitude of evoked field excitatory postsynaptic potentials (fEPSPs) recorded from hippocampal CA1 neurons was examined in anaesthetized rats with a unilateral common carotid artery occlusion. The amplitudes of fEPSPs recorded from the hippocampus ipsilateral to the occlusion were significantly more depressed with hypoxia than were the fEPSPs recorded from the contralateral hippocampus. The adenosine A1-selective antagonist, 8-cyclopentyl-1,3-dimethylxanthine (8-CPT), blunted the hypoxic depression of the fEPSP. Tissue partial pressure of oxygen (Ptiss,O2) was measured in the ipsilateral and contralateral hippocampus using glass Clark-style microelectrodes. Ptiss,O2 fell to similar levels as a function of inspired oxygen in the ipsilateral and contralateral hippocampus, and in the ipsilateral hippocampus after administration of 8-CPT. Hippocampal blood flow (HBF) was measured using laser Doppler flowmetry. A decline in HBF was associated with systemic hypoxia in both hippocampi. HBF, as a function of inspired oxygen, fell significantly more in the ipsilateral than in the contralateral hippocampus. We conclude that endogenous adenosine acting at the neuronal A1 receptor plays a major role in the depression of synaptic transmission during hypoxic ischaemia. The greater susceptibility of the fEPSP in the ipsilateral hippocampus to systemic hypoxia cannot be explained entirely by differences in Ptiss,O2 or HBF between the two hemispheres.
Fowler
J C
JC
Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. phyjcf@ttuhsc.edu
Gervitz
L M
LM
Hamilton
M E
ME
Walker
J A
JA
D000241:Adenosine / Q000502:physiology; D000818:Animals; D002339:Carotid Arteries / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D017078:Laser-Doppler Flowmetry; D008297:Male; D010100:Oxygen / Q000097:blood; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline; D000241:Adenosine; D010100:Oxygen