Loop C proline mutations generate PO modes. WT AChR clusters are homogenous. (A; left) Single-channel currents (30 µM ACh; −100 mV; open is down). Clusters of openings are binding-gating events (C-O) and long silent intervals between clusters are desensitization (D). (Right) Histograms of cluster PO (fitted by a single Gaussian) and intra-cluster interval durations (fitted by a single exponential). (Inset) An example cluster. In both adult and fetal AChRs, there is only a single PO population (0.70 ± 0.06, 187, and 0.93 ± 0.03, 156; mean ± SD; n clusters). (B) Loop C mutations αP197A and αP194A in adult AChRs induce modes. PO histograms for αP197A have four populations (0.01 ± 0.01, 83; 0.20 ± 0.04, 6; 0.67 ± 0.06, 8; and 0.96 ± 0.01, 110), and multiple exponentials are required to describe the interval duration distributions.
