Figure 8.
ATR appears to prefer closed, unliganded channels, and to interfere with channel opening. ATR dose–response relations for homomeric (CNGA1) channels activated by cGMP or cAMP. (A) Data were measured as described in Fig. 2 for ATR dose–response curves in saturating (2 mM) cGMP (blue filled circles), saturating (20 mM) cAMP (red squares; giving only 5% of the activation obtained with 2 mM cGMP), and low (∼10–15 μM) cGMP (green open circles; giving ∼7.4% of the activation obtained with 2 mM cGMP). Error bars are SEM values. Averaged data points from 2–7 patches were normalized to Io and fit with the model (B) described above (see materials and methods and results), where K1 = 9.0 × 1010 M−n, K2 = 4.0 × 1010 M−n, K3 = 2.8 × 1010 M−n, K4 = 2.0 × 109 M−n, and n = 1.43. For saturating and low cGMP, L = 19.8 and KcN = 7,200 M−1; for cAMP, L = 0.055 and KcN = 1,144 M−1. The red dashed line represents the prediction of the model for cAMP if ATR binding depends only on the open probability and not on ligand occupancy (i.e., K1 = K2 = K3 = 9 × 1010 M−n).