Human 5-HT3A -- Ser 292
|Rat Equivalent||Ser 291|
|Mouse Equivalent||Ser 297||Cys||S297C|
This mutation (S19'R or SR) produced functional 5-HT gated receptors. When it was doubly mutated with E272A (E-1'A or EA), functional receptors were also generated. The Ec50 values for 5-HT and retification properties were similar to those of WT receptors. The activation kinetics were also similar, but the desensitization rates did vary in that the time constant for SR was less than the WT. The double mutation EASR caused a greater decrease in the time constant. (WT>EA>SR>EASR)
However, when it was combined with A297K (either SR alone or EASR), no functional receptors were detected.
The SR receptors were shown to be cation selective, where as the EA receptors showed no selectivity. However, the EASR receptors appeared to be anionic.
Thompson AJ, Lummis SCR (2003) A Single Ring of Charged Amino Acids at One End of the Pore Can Control Ion Selectivity in the 5-HT3 Receptor. British Journal of Pharmaoclogy 140(s) 359-365
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After the application of 1mM MTSET with 10uM 5-HT, there was no significant change. After the application of 1mM MTSES with 10uM 5-HT, there was no significant change.
Reeves DC, Goren EN, Akabas MH, Lummis SCR (2001) Structural and Electrostatic Properties of the 5-HT3 Receptor Pore Revealed by Substituted Cysteine Accessibility Mutagenesis. The Journal of Biological Chemistry 276(45):42035-42042
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