Purinergic fast excitatory postsynaptic potentials in myenteric neurons of guinea pig: Distribution and pharmacology

Abstract

Background and Aims: Adenosine triphosphate (ATP) acting at P2 receptors mediates some fast excitatory postsynaptic potentials (fEPSPs) in myenteric neurons of guinea pig ileum. The present studies investigate the distribution of purinergic fEPSPs along the length of the gut and characterize the P2- receptor subtype mediating fEPSPs. Methods: Conventional intracellular electrophysiological methods were used to record from myenteric neurons in vitro. Results: At a membrane potential of -97 ± 1 mV, the amplitude (25 ± 1 mV; n = 307) of fEPSPs was similar along the gut. Hexamethonium (100 μmol/L) inhibited fEPSPs in the gastric corpus by 98% ± 1% (n = 31) and in the duodenum, ileum, taenia coli, proximal colon, and distal colon by 42%- 55%. In the presence of hexamethonium, suramin (100 μmol/L) or the P2X antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 10 μmol/L) reduced the control fEPSP amplitude in the duodenum, ileum, taenia coli, proximal colon, and distal colon by 71%-84%. The pharmacology of the purinergic fEPSPs was investigated in detail in the ileum. Noncholinergic fEPSPs were concentration-dependently (1-30 μmol/L) inhibited by PPADS (50% inhibitory concentration, 3 μmol/L). In addition, α,β-methylene 5'- adenosine triphosphate (1 μmol/L) also reduced purinergic fEPSPs. Conclusions: Fast EPSPs mediated in part through P2X receptors are prominent in myenteric neurons along the small and large intestines but are rare in the gastric corpus.