Elevation of adenosine 3',5'-phosphate mimics slow synaptic excitation in myenteric neurones of the guinea-pig

Abstract

Intracellular recording was used to assess the effects of elevation of intraneuronal adenosine 3',5'-phosphate (cyclic AMP) on electrical behaviour of AH/Type 2 myenteric neurones in guinea-pig small intestine. Intracellular injection of cyclic AMP resulted in membrane depolarization, increased input resistance, suppression of post-spike hyperpolarizing potentials and enhanced excitability. Application of 8-(4-chlorophenylthio) cyclic AMP or 8-bromo cyclic AMP, which are membrane permeant analogues of cyclic AMP, resulted in the same changes in electrical behaviour as intracellular injection of cyclic AMP. Treatment with the phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine, resulted in the same changes in neuronal electrical behaviour as intracellular injection of cyclic AMP and application of permeable analogues of cyclic AMP. Each of the treatments, which were expected to elevate intraneuronal cyclic AMP, duplicated the electrophysiological behaviour of AH/Type 2 neurones during slow synaptic excitation. The results support the hypothesis that the biochemical basis for slow synaptic excitation in AH/Type 2 myenteric neurones of guinea-pig small intestine is increased synthesis of cyclic AMP in the cell soma.