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Vol. 290, Issue 2, 803-810, August 1999
Department of Pharmacology and Toxicology and the Neuroscience
Program, Michigan State University, East Lansing, Michigan
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 (
1 = 1.1 ± 0.1 s;
2 = 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.
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