Mechanism of adenosine accumulation in the hippocampal slice during energy deprivation.


Journal Article

The mechanism by which adenosine accumulates in the hippocampal slice during energy deprivation was investigated by examining the adenosine A1 receptor mediated depression of synaptically evoked field potentials in the CA1 area. Blocking of the mitochondrial electron transport chain with 200 microM sodium cyanide or mitochondrial uncoupling with 50 microM 2,4-dinitrophenol both produced a rapid depression of synaptic transmission that was antagonised by 1 microM 8-cyclopentyl-1, 3-dimethylxanthine, an adenosine A1 receptor antagonist. Cellular ATPase inhibition or elevation of cytosolic phosphocreatine failed to alter the 2,4-dinitrophenol induced depression of synaptic transmission. Attempts to block mitochondrial ATP synthesis with 3 microM oligomycin or 75 microM atractyloside did not cause depression of synaptic transmission. 100 microM iodotubercidin, an adenosine kinase inhibitor, alone produced a depression of synaptic transmission that was completely reversed by 1 microM 8-cyclopentyl-1,3-dimethylxanthine; however, a simultaneous or independent episode of hypoxia surmounted the adenosine A1 receptor antagonism and produced approximately 50% depression of synaptic transmission. Depression of synaptic transmission by hypoxia, cyanide or 2,4-dinitrophenol is a result of rapid adenosine accumulation and activation of extracellular adenosine A1 receptors. Although this early depression of synaptic transmission is a consequence of inhibition of normal mitochondrial function, it is not a result of depletion of cytosolic ATP, since attempts to preserve ATP did not maintain synaptic transmission during mitochondrial poisoning, and inhibitors of oxidative phosphorylation did not produce synaptic depression.

Full Text

Cited Authors

  • Doolette, DJ

Published Date

  • February 1997

Published In

Volume / Issue

  • 30 / 2

Start / End Page

  • 211 - 223

PubMed ID

  • 9017669

Pubmed Central ID

  • 9017669

Electronic International Standard Serial Number (EISSN)

  • 1872-9754

International Standard Serial Number (ISSN)

  • 0197-0186

Digital Object Identifier (DOI)

  • 10.1016/s0197-0186(96)00055-1


  • eng