Human 5-HT3A -- Arg 432

Species Original Mutated to Mutation
Human Arg 432 Gln

R432Q

Rat Equivalent Arg 431    
Mouse Equivalent Arg 437    

hArg432Gln

This mutation had little effect on the single-channel conductance. When it was combined with R436D, the double mutation produced conductance that was greater than the sum of the individual mutations. When it was combined with R440A, there was no such synergy. In a triple mutation of R432Q, R436D, and R440A, the single-channel conductance increased substantially.

Kelley SP, Dunlop JI, Kirkness EF, Lambert JJ, Peters JA (2003) A Cytoplasmic Region Determines Single-Channel Conductance in 5-HT3 Receptors. Nature 424(6946):321-324

 

In this study the cytoplasmic membrane-associated (MA) helix arginine residues 432 (-4'), 436 (0'), and 440 (4') of a homomeric 5HT3AR were replaced with equivalent residues found in 5HT3B to determine if these mutations had any effect on single channel conductance (γ). The techniques of whole-cell and outside-out patch recording were used to measure γ indirectly (by variance analysis) and directly (from single channel amplitudes), respectively. The study concluded that the MA 0' position had the greatest effect on γ.

The R432Q mutation had no significant effect on γ. The R432Q, R436D two-point mutation caused an ~18-fold increase in γ. The R432Q, R440A two-point mutation caused an ~7-fold increase in γ. The R432Q, R436D, R440A three-point mutation caused an ~38-fold increase in γ. The R432Q, R436E, R440A three-point mutation caused an ~36-fold increase in γ. The R432Q, R436Q, R440A three-point mutation caused an ~24-fold increase in γ. The R432Q, R436F, R440A three-point mutation caused an ~2-fold increase in γ.

Hales TG, Dunlop JI, Deeb TZ, Carland JE, Kelley SP, Lambert JJ, Peters JA (2006) Common Determinants of Single Channel Conductance within the Large Cytoplasmic Loop of 5-Hydroxytryptamine Type 3 and α4β2 Nicotinic Acetylcholine Receptors. The Journal of Biological Chemistry 281(12):8062-71

 

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