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Nature. 1989 Jun 29;339(6227):706-9.

5-HT3 receptors are membrane ion channels.

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Vollum Institute, Oregon Health Sciences University, Portland 97201.


The neurohormone 5-hydroxytryptamine (5HT or serotonin) exerts its effects by binding to several distinct receptors. One of these is the M-receptor of Gaddum and Picarelli, now called the 5-HT3 receptor, through which 5-HT acts to excite enteric neurons. Ligand-binding and functional studies have shown that the 5-HT3 receptor is widely distributed in peripheral and central nervous tissue and evidence suggests that the receptor might incorporate an ion channel permeable to cations. We now report the first recordings of currents through single ion channels activated by 5-HT3 receptors, in excised (outside-out) membrane patches from neurons of the guinea pig submucous plexus. Whereas application of acetylcholine activated predominantly a 40-pS channel, 5-HT caused unitary currents apparently through two channels of conductances of 15 and 9 pS, which were reversibly blocked by antagonists of the 5-HT3 receptor. Receptors for amine neurotransmitters, including 5-HT1 and 5-HT2, have previously been thought to transduce their effects through GTP-binding proteins: the direct demonstration that 5-HT3 receptors are ligand-gated ion channels implies a role for 5-HT, and perhaps other amines, as a 'fast' synaptic transmitter.

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