Extracellular adenosine 5′-triphosphate plus activation of glutamatergic receptors induces long-term potentiation in CA1 neurons of guinea pig hippocampal slices

Abstract

The mechanism of adenosine 5′-triphosphate (ATP)-induced long-term potentiation (LTP) was studied pharmacologically using guinea pig hippocampal slices. Application of 10 μM ATP for 10 min transiently depressed, then slowly augmented, synaptic transmission in CA1 neurons, leading to LTP. This ATP-induced LTP was blocked by addition of an N-methyl- d-aspartate (NMDA) glutamate receptor antagonist. Furthermore, co-application of 10 μM ATP and 100 μM l-glutamate for 10 min also induced LTP, and this effect was blocked by the use of Ca 2+-free solution during drug application. These results suggest that, in CA1 neurons, a co-operative effect involving extracellular ATP and the activation of NMDA receptors, which increases intracellular Ca 2+ levels, is required to trigger the intracellular biological process involved in ATP-induced LTP.