Abstract
5-hydroxytryptamine receptor subtype 3 (5-HT3R) is a pentameric ligand-gated ion channel (pLGIC) involved in neuronal signaling. It is best known for its prominent role in gut-CNS signaling though there is growing interest in its other functions, particularly in modulating non-serotonergic synaptic activity. Recent advances in structural biology have provided mechanistic understanding of 5-HT3R function and present new opportunities for the field. This chapter gives a broad overview of 5-HT3R from a physiological and structural perspective and then discusses the specific details of ion permeation, ligand binding and allosteric coupling between these two events. Biochemical evidence is summarized and placed within a physiological context. This perspective underscores the progress that has been made as well as outstanding challenges and opportunities for future 5-HT3R research.
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