Table 1 Effects of amino acid replacements on ligand responses in human and Epipedobates high-ACh sensitivity (HS) nAChRs.

Relative fold change in sensitivity induced by amino acid replacements was calculated as (mutant EC50)/(FSAI EC50) for each genetic background [i.e., (mutant)/(reference); see tables S5 to S7] (24). Values greater than 1 indicate that relatively more ligand is required to elicit the same response; thus, higher values indicate lower sensitivity. ACh assessments for biphasic curves (>1) are qualitative, but both cases result in lowered sensitivity (see tables S5 and S6) (24). *P < 0.01; **P < 0.001 (two-way analysis of variance, corrected for multiple comparisons using Tukey’s test; see tables S9, S11, S13, and S14) (24).

Human genetic backgroundEpipedobates genetic background
GenotypeAmino acid
replacement(s)
Fold change
in EC50 ACh
Fold change in
EC50 epibatidine
GenotypeAmino acid
replacement(s)
Fold change
in EC50 ACh
Fold change
in EC50 epibatidine
FSAI(Wild-type)ReferenceReferenceFSAIL106F
C108S
ReferenceReference
LCAIF106L
S108C
117**LCAI(Wild-type)144**
LSAIF106L11LSAIC108S11
FCAIS108C>149**FCAIL106F2*138**
FCVVS108C
A110V
I118V
16**
FSVIA110V11
FSAVI118V>175**