Serotonin 5‐HT 3 receptors in rat CA1 hippocampal interneurons: functional and molecular characterization

• Published in: The Journal of physiology 2002-11, Vol.544 (3), p.715-726
• Main Authors: Sudweeks, Sterling N., van Hooft, Johannes A., Yakel, Jerrel L.
• Format: Article
• Language: English
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2002.029736

The molecular makeup of the serotonin 5‐HT 3 receptor (5‐HT 3 R) channel was investigated in rat hippocampal CA1 interneurons in slices using single‐cell RT‐PCR and patch‐clamp recording techniques. We tested for the expression of the 5‐HT 3A (both short and long splice variants) and 5‐HT 3B subunits, as well as the expression of the α4 subunit of the neuronal nicotinic ACh receptors (nAChRs), the latter of which has been shown to co‐assemble with the 5‐HT 3A subunit in heterologous expression systems. Both the 5‐HT 3A ‐short and α4‐nAChR subunits were expressed in these interneurons, but we could not detect any expression of either the 5‐HT 3B or the 5‐HT 3A ‐long subunits. Furthermore, there was a strong tendency for the 5‐HT 3A ‐short and α4‐nAChR subunits to be co‐expressed in individual interneurons. To assess whether there was any functional evidence for co‐assembly between the 5‐HT 3A ‐short and α4‐nAChR subunits, we used the sulphydryl agent 2‐aminoethyl methanethiosulphonate (MTSEA), which has previously been shown to modulate expressed 5‐HT 3 Rs that contain the α4‐nAChR subunit. In half of the interneurons examined, MTSEA significantly enhanced the amplitude of the 5‐HT 3 R‐mediated responses, which is consistent with the notion that the α4‐nAChR subunit co‐assembles with the 5‐HT 3A subunit to form a native heteromeric 5‐HT 3 R channel in rat CA1 hippocampal interneurons in vivo . In addition, the single‐channel properties of the 5‐HT 3 R were investigated in outside‐out patches. No resolvable single‐channel currents were observed. Using non‐stationary fluctuation analysis, we obtained an estimate of the single‐channel conductance of 4 pS, which is well below that expected for channels containing both the 5‐HT 3A and 5‐HT 3B subunits.