Extracellular ATP reduces optically monitored electrical signals in hippocampal slices through metabolism to adenosine

Electrical signals in rat hippocampal slices were optically monitored using a voltage-sensitive dye to determine whether extracellular ATP exhibits direct effects through its own receptors or indirect effects after its hydrolysis to adenosine. The dentate gyrus was stimulated and electrical signals in the CA1 and the CA3 region were analyzed. The signals were divided into two components: a transient component peaking within 10 ms (fast component) and a subsequent sustained component (slow component). ATP (10 to 100 mu M) inhibited both the fast and the slow components in the CA1 region by about 30% and 70%, respectively. ADP, AMP and adenosine also inhibited the fast and the slow components. The inhibition by ATP was antagonized by aminophylline and other adenosine receptor antagonists, and by alpha,beta-methylene ADP, an inhibitor of 5'-nucleotidases. These results suggest that extracellular ATP inhibits neuronal electrical signals in hippocampal slices after its metabolism to adenosine. (C) 2000 Elsevier Science B.V. All rights reserved.