Blocking action of adenosine and ATP on synaptic transmission in isolated rat brain slices

Abstract

The effect of ATP and adenosine on spontaneous activity and orthodromic responses of single neurons and on global evoked potentials was investigated in surviving slices of rat neocortex, hippocampus, dentate fascia, and cerebellumin vitro. ATP and adenosine, added to the incubation medium, had a twofold action on neurons: excitatory and inhibitory. Excitation was observed only if high concentrations of the substances (10−2, less frequently 10−3 M) were used, and in the case of adenosine it was very weak. The excitatory effect is evidently due to the direct depolarizing action of these substances on the cell membrane. The inhibitory action of both ATP and adenosine was manifested even in low concentrations (10−6–10−7 M) and was expressed as inhibition of postsynaptic responses of neurons at the presynaptic level and of their spontaneous activity. Hippocampal neurons were most sensitive to these substances, cerebellar neurons least. Apamine was found to have no effect on the inhibitory action of ATP. The results do not support the view that ATP and adenosine may be classed as CNS neurotransmitters. The possible role of these drugs as neuromodulators of synaptic transmission in the CNS is discussed.