Serotonin Gate (5-HT3R)

This page is about the single serotonin ionotropic receptor.  For the multiple serotonin metabotropic receptors and a discussion of the naming conventions for serotonin receptors,
Serotonin Metabotropic Receptor

Cross reference: 
Rodent 5-HT3R

Serotonin (Wiki) 
"Serotonin or 5-Hydroxytryptamine (5-HT) is
a monoamine neurotransmitter, biochemically derived from tryptophan

5-HT3 receptor (Wiki) 
    "The 5-HT3 receptor is a member of the superfamily of ligand-gated ion channels, a superfamily that also includes the neuronal nicotinic acetylcholine receptors (nAChRs), and the inhibitory neurotransmitter receptors for GABA (both GABAA and GABAA receptors) and glycine.[1][2]  The 5-HT3 receptor is most closely related by homology to the nicotinic acetylcholine receptor.
The 5-HT3 receptor consists of 5 subunits arranged around a central ion conducting pore, which is permeable to sodium, potassium, and calcium ions. Binding of the
neurotransmitter 5-hydroxytryptamine (serotonin) to the
5-HT3 receptor opens the channel, which, in turn, leads to an excitatory response in neurons. The 5-HT3 receptor differs markedly in structure and mechanism from the other 5-HT receptor subtypes, which are all G-protein-coupled.

5-HT3 Receptors (PubMed) 
Full length HTML and PDF available online for free. 
5-HT3 receptors are ligand-gated ion channels (LGIC) and therefore differ from all other 5-HT (serotonin) receptors whose actions are mediated via G proteins. Their structure and function has placed them in the Cys-loop family of ligand-gated ion channels. Similar to other members of this family, the 5-HT3 receptor is composed of five symmetrically arranged subunits that surround a central ion-conducting pore (Fig. (1)). The 5-HT3A receptor subunit is able to form functional homomeric receptors, and also combines with the more recently cloned 5-HT3B subunit to create hetero-pentamers that display distinct electrical and pharmacological properties [1, 2]. Genes for 5-HT3C, 5-HT3D and 5-HT3E subunits have also been described, but to date these subunits have not been characterised [3].

Actions of general anaesthetics on 5-HT3 receptors in N BE- 15 neuroblastoma cells (Goog) 
Full length PDF available online for free. 
"The 5-HT3 receptor is a member of the genetically related superfamily of ligand-gated receptor-channels that also includes the GABAA receptor, the glycine receptor, and neuronal and muscle-type nicotinic acetylcholine (ACh) receptors. ... Furthermore, a recent molecular evolution analysis has concluded that the 5-HT3 receptor is one of the most primitive members of this superfamily of ligand-gated receptor-channels."

Physiology and pathophysiology of the 5-HT3 recept (PubMed) 
Only abstract available online. 
5-HT3 receptors modulate the release of neurotransmitters and neuropeptides like dopamine, cholecystokinin, acetylcholine, GABA, substance P, and serotonin itself.

The 5-HT3 receptor--the relationship between structure and function (PubMed)   
Only abstract available online. 
The 5-hydroxytryptamine type-3 (5-HT3) receptor is a cation-selective ion channel of the Cys-loop superfamily. 5-HT3 receptor activation in the central and peripheral nervous systems evokes neuronal excitation and neurotransmitter release.

Serotonin Receptors(Goog) 
No abstract online.  I got the PDF through the library. 
"In contrast to all of the other serotonin receptors, which are GPCRs, the 5-HT3 receptor is a cation-selective ion channel of the cysteine-loop transmitter-gated superfamily of ligandgated ion channels that includes the acetylcholine nitotinic receptor, the anion-selective GABAA receptor, and glycine receptor."   

The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand-gated ion channel (review) (PubMed) 
Only abstract available online.  
The ligand-gated ion channel superfamily of neurotransmitter receptors are proteins responsible for rapid transmission of nerve impulses at the synapse ... The cys-loop family, of which the 5-HT3 receptor is a member, includes the nicotinic acetylcholine receptor, the GABAA receptor and the glycine receptor. ... the family shares many similarities of structure and function.

Serotonin (5-HT) Receptor (Goog - Wiki) 

Family Type Mechanism Potential
5-HT1 Gi/Go-protein coupled. Decreasing cellular levels of cAMP. Inhibitory
5-HT2 Gq/G11-protein coupled. Increasing cellular levels of IP3 and DAG. Excitatory
5-HT3 Ligand-gated Na+ and K+ cation channel. Depolarizing plasma membrane. Excitatory
5-HT4 Gs-protein coupled. Increasing cellular levels of cAMP. Excitatory
5-HT5 Gi/Go-protein coupled.[4] Decreasing cellular levels of cAMP. Inhibitory
5-HT6 Gs-protein coupled. Increasing cellular levels of cAMP. Excitatory
5-HT7 Gs-protein coupled. Increasing cellular levels of cAMP. Excitatory

My comment
Of course, it's important to remember that the
polarity of the response of the entire animal to the activation of the receptor, i.e., whether it's excitatory or inhibitory, may not be the same as the polarity of the neuron's response to activation of the receptor. 

For example, if a 5-HT1 receptor is activated, it will inhibit the neuron on whose membrane it resides.  However, if the neuron expressing the 5HT-1 receptor is itself inhibitory in its output, for example, if the neuron is GABAergic, the final outcome of activation of the inhibitory receptor will be excitation of the downstream neuron which was being inhibited by the neuron bearing the 5-HT1 receptor. 

Unfortunately, this only tells us what's there, not how it's all hooked together.  Until we know the wiring diagram, the polarity of the individual receptors doesn't tell us much about the animal's final behavior. 

22. - from PubMed search:   Accumbens Frontal GABA

Physiology and pathophysiology of the 5-HT3 receptor.

Färber L, Haus U, Späth M, Drechsler S.

Scand J Rheumatol Suppl. 2004;119:2-8. Review.

[PubMed - indexed for MEDLINE]
Related citations

Please see: Amphioxus Serotonin System and  Rodent Hormone-Nerve Interaction for more information and comments on the 5-HT3 receptor.