Table 2.

Parametric comparisons of dose–response relationships to 5-HT generated in wild-type and conditional smooth muscle–specific ANO1 KO mice

EC50 (nM)Maximum 5-HT contraction amplitude (normalized to KCl)Slope factor pNMean R2
Wild-type
Control 209 ± 34 0.784 ± 0.073 1.57 ± 0.25 14 0.993 ± 0.004 
ANO1-KO Δ exon 12      
Oil-injected control 210 ± 36 0.771 ± 0.105 1.14 ± 0.17 0.993 ± 0.002 
TMX-injected 125 ± 24 0.250 ± 0.034a,b 1.54 ± 0.31 0.981 ± 0.008 
ANO1-KO Δ exons 5/6      
TMX-injected 195 ± 72 0.316 ± 0.056a,c 0.96 ± 0.15 0.924 ± 0.062 

Individual dose–response curves to 5-HT were least-square fitted to a logistic function of the following formalism: Y = A1 + [(A2 − A1)/(1 + ([5-HT]/EC50)p)], where Y is the contraction amplitude registered in the presence of 5-HT normalized to the high KCl-induced contraction, A1 and A2 are the minimum and maximum contraction amplitudes, respectively, [5-HT] is the concentration of 5-HT, EC50 is the concentration of 5-HT producing a contraction that is 50% of maximum, and p is the slope factor. Because of the biphasic nature of the dose–response curves to 5-HT (see Fig. 1 and text for explanation), only the initial portion of each curve, thus ranging from 0.01 to 3 μM 5-HT, was analyzed to calculate the parameters shown in the table. All values are means ± SEM pooled from 4 to 14 animals (N). One-way ANOVA tests revealed significant differences in the maximum contraction amplitude between animal groups as shown (bolded numbers).

a

P < 0.01 versus wild-type control.

b

P < 0.01 versus ANO1-KO Δ exon 12.

c

P < 0.05 versus ANO1-KO Δ exon 12.

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