Figure 5. Effect of combined exposure to CPT-cAMP and CPT-cGMP on cytotoxicity of cells expressing channels with disease-associated mutations in CNGB3. A: Representative dose–response relationships for CPT-cAMP activation of CNG channels, after coexpression of CNGA3 with CNGB3-WT (circles), T383fsX (squares), or F525N (triangles) subunits (same representative patches as in Figure 1B). Currents were normalized to the maximum CPT-cGMP current. Continuous curves represent fits of the dose–response relationship with the Hill equation. Parameters for each channel type were as follows: for WT, K_1/2,CPT-cAMP=28.3 μM and h=1.4; for T383fsX, K_{1/2, cAMP}=27.9 μM and h=1.6; and for F525N, K_1/2,CPT-cAMP=10.8 μM and h=1.0. B: Bar graph of the relative cytotoxicity for channel-expressing cells exposed to various concentrations of CPT-cAMP plus 0.1 μM CPT-cGMP (n=12). The dashed line represents the percentage of cell death in the vector-only control group without treatment; * indicates significant difference between groups designated by bracket (p<0.05); + represents significant difference between the F525N group treated with 10 μM CPT-cAMP together with 0.1 μM CPT-cGMP and the F525N group without treatment (p<0.01).