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.
Peters
John A
JA
Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, The University of Dundee, Dundee DD1 9SY, UK. j.a.peters@dundee.ac.uk
Hales
Tim G
TG
Lambert
Jeremy J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007477:Ions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D007473:Ion Channels; D007477:Ions; D011978:Receptors, Nicotinic; D044406:Receptors, Serotonin, 5-HT3; D003545:Cysteine