Primary Structure And Functional Expression of the 5HT ₃ Receptor, A Serotonin-gated Ion Channel

TLDR

Serotonin activates both second‑messenger signaling pathways and ion channels directly, enabling rapid excitatory responses. A cDNA clone encoding a 5HT3 receptor subtype was isolated from a neuroblastoma library and functionally expressed in Xenopus oocytes to produce serotonin‑gated currents. The cloned receptor shares ligand‑gated ion channel features, displays pharmacology and electrophysiology matching native 5HT3 receptors, is expressed in brain, spinal cord, and heart, and establishes a new class of excitatory ligand‑gated channels.

Abstract

The neurotransmitter serotonin (5HT) activates a variety of second messenger signaling systems and through them indirectly regulates the function of ion channels. Serotonin also activates ion channels directly, suggesting that it may also mediate rapid, excitatory responses. A complementary DNA clone containing the coding sequence of one of these rapidly responding channels, a 5HT3 subtype of the serotonin receptor, has been isolated by screening a neuroblastoma expression library for functional expression of serotonin-gated currents in Xenopus oocytes. The predicted protein product has many of the features shared by other members of the ligand-gated ion channel family. The pharmacological and electrophysiological characteristics of the cloned receptor are largely consistent with the properties of native 5HT3 receptors. Messenger RNA encoding this receptor is found in the brain, spinal cord, and heart. This receptor defines a new class of excitatory ligand-gated channels.