Molecular determinants of single-channel conductance and ion selectivity in the Cys-loop family: insights from the 5-HT3 receptor

The molecular determinants of the ionic selectivity and single-channel conductance of the Cys-loop family of transmitter-gated ion channels are beginning to be understood with increasing precision, in part, as a result of the recent availability of refined ultrastructural information for the archetype of the family, the nicotinic acetylcholine receptor (nAChR). Studies of another member of this family, the 5-HT(3) receptor, have now provided insight into the structure of its channel pore, the location of its gate and mechanisms of ion selectivity and translocation. The anomaly of the extremely low single-channel conductance of the homo-oligomeric 5-HT(3A) receptor has recently been solved, revealing that an intracellular domain of the protein is an important determinant of single-channel conductance. Such data are interpreted, in this article, in light of the most recent developments in structural characterization of the nAChR.