Extensive BD sequence substitutions preserve con action. (A) Topology of the CNG channel subunit, highlighting the BD region substituted in the X-chimera series of constructs. Alignment compares the substituted BD sequences (bounded by vertical dotted lines) originating from rCNGA4 (in X-rA4) and fCNGA2 (in X-fA2). Invariant non-BD sequences (Young et al., 2001) include bCNGA1 sequence in the C-linker and the extreme C-terminal region, respectively, before and after the BD. Dots in the sequence alignment indicate fCNGA2 residues conserved with rCNGA4; secondary structure elements are marked (α for helices, β for strands) as predicted by comparative modeling (Fig. 4). (B) X-chimera testing substitutions in the C-terminal portion of the BD. Bar represents BD sequence; below the bars, secondary structure elements are marked (letters for helices, numbers for strands, and PB for the PB cassette). Gray background color in bar represents amino acids conserved between fCNGA2 and rCNGA4; black ticks mark unconserved amino acids found in fCNGA2 but not in rCNGA4. Mean g_{(10 mM cGMP)}/g_{(3 mM cGMP)} values (±SD, number of patches in parentheses) include those previously reported for Construct 1 (Young et al., 2001) and for Construct 2 and X-rA4 (Chan and Young, 2009). (C) Examples of current traces for selected constructs during 10-mM cGMP pulses, with g_{(10 mM cGMP)}/g_{(3 mM cGMP)} as marked (based on applications of 3 mM cGMP; not depicted). Horizontal bar, 10 s; vertical bar, 1 nA.