Synaptic activation and properties of 5-hydroxytryptamine(3) receptors in myenteric neurons of guinea pig intestine.
The contribution of 5-hydroxytryptamine (serotonin; 5-HT) acting at 5-HT(3) receptors to fast excitatory postsynaptic potentials (fEPSPs) and the properties of 5-HT(3) 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 microM) inhibited hexamethonium (100 microM)-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 (tau1 = 1.1 +/- 0.1 s; tau2 = 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 microM) and partly inhibited by d-tubocurare (1 microM). The 5-HT(3)-receptor agonist, 2-methyl-5-HT (100 microM), caused a peak current that was 18% of the peak current caused by 5-HT in the same cells; 2-methyl-5-HT (1 microM) 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-HT(3) receptor expressed by guinea pig myenteric neurons has pharmacological and electrophysiological properties that distinguish it from 5-HT(3) receptors expressed by other autonomic neurons and neurons in the central nervous system.
Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Michigan, USA.
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Zhou
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Galligan
D000818:Animals; D046508:Culture Techniques; D004594:Electrophysiology; D006168:Guinea Pigs; D007421:Intestine, Small / Q000187:drug effects / Q000294:innervation*; D007700:Kinetics; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; C045918:2-methyl-5-HT