Hyperexcitability in CA1 of the rat hippocampal slice following hypoxia or adenosine.
Participation of adenosine receptors in the depression of synaptic transmission during hypoxia, and the production of multiple populations spikes in the pyramidal neurons following hypoxia, has been investigated in the CA1 area of the rat hippocampal slice. A method is presented for analysing such hyperexcitability, using input/output curves of the second population spike. This method provides evidence that rebound hyperexcitability following hypoxia or prolonged adenosine-mediated inhibition results from an increase in excitability of the CA1 pyramidal neurons rather than from an increase in excitatory neurotransmitter release. Hypoxia-induced depression of the synaptic components of evoked field potentials was blocked in a concentration dependent manner by the selective A1 receptor antagonist 8-cyclopentyltheophylline (8-CPT), demonstrating extracellular accumulation of adenosine during hypoxia. Upon reoxygenation of slices following 30 min hypoxia, multiple population spikes were evoked by a single orthodromic stimulus in slices that exhibited only a single population spike prior to hypoxia. Such post-hypoxic hyperexcitability was not prevented by superfusion of slices with 8-CPT during hypoxia. Depression of synaptic transmission by 30 min superfusion of slices with 50 microM adenosine was also followed, upon washout, by the appearance of multiple population spikes. However, such hyperexcitability could not be produced by superfusion with adenosine analogues selective for A1 receptors, cyclopentyladenosine, selective for A2a receptors, 2-p-(2-carboxyethyl)phenetheylamino-5'-ethylcarboxamidoadenosine (CGS 21680), or active at A2a and A2b receptors, N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine, suggesting that adenosine receptors other than the A1, A2a or A2b subtypes are involved in its generation.
Doolette
D J
DJ
Department of Anaesthesia and Intensive Care, University of Adelaide, Australia.
Kerr
D I
DI
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D000241:Adenosine