Synaptic Activation and Properties of 5-Hydroxytryptamine₃ Receptors in Myenteric Neurons of Guinea Pig Intestine1

Abstract

The contribution of 5-hydroxytryptamine (serotonin; 5-HT) acting at 5-HT₃ receptors to fast excitatory postsynaptic potentials (fEPSPs) and the properties of 5-HT₃ receptors in the guinea pig small intestinal myenteric plexus were investigated using electrophysiological methods. In 11% of neurons studied in the acutely isolated myenteric plexus, ondansetron (1 μM) inhibited hexamethonium (100 μM)-resistant fEPSPs. 5-HT elicited an inward current in neurons maintained in primary culture. The peak current reached maximum in <150 ms and desensitized with a double exponential time course (τ1 = 1.1 ± 0.1 s; τ2 = 6.9 ± 0.9 s). The whole-cell current/voltage relationship was linear, with a reversal potential of 2.7 ± 1.5 mV. The rapidly activating and desensitizing current was completely blocked by ondansetron (1 μM) and partly inhibited by d-tubocurare (1 μM). The 5-HT₃-receptor agonist, 2-methyl-5-HT (100 μM), caused a peak current that was 18% of the peak current caused by 5-HT in the same cells; 2-methyl-5-HT (1 μM) inhibited currents caused by 5-HT. 5-HT-activated single-channel currents in outside-out patches; this response was blocked by ondansetron. The single-channel conductance was 17 ± 1 pS. The single-channel current/voltage relationship was linear between −110 and 70 mV and had a reversal potential near 0 mV. These data indicate that 5-HT contributes to fEPSPs in the myenteric plexus. The 5-HT₃ receptor expressed by guinea pig myenteric neurons has pharmacological and electrophysiological properties that distinguish it from 5-HT₃ receptors expressed by other autonomic neurons and neurons in the central nervous system.