Xenbase Image ID: 159291

Figure 5. Disease hotspot position 508 is on the move in the transition state for opening.(A), Inward unitary currents of the cut-ΔR(D1370N) CFTR background construct, and of channels bearing mutations at position 508, in the same background. Letters to the left of the traces indicate the amino acid present in the target position; the native residue is marked by red. Currents were recorded at −80 mV, in symmetrical 140 mM Cl-; dashes on the left mark zero-current level. (B–D) Mean burst (B, τb) and interburst (C, τib) durations and open probabilities (D, Po) of the constructs in (A). Red horizontal lines highlight the respective control values of the background construct which is identified by the red letter representing the native target residue. All data are shown as mean ± SEM (n = 5–7). E, Brønsted plot for position 508. Red symbol and letter identifies the background construct. Solid line is a linear regression fit with slope Φ indicated.Figure 5—figure supplement 1. Burst analysis of single-channel recordings for position 508 mutants.(A, F) Inward currents of single cut-ΔR(D1370N) channels bearing mutation F508S (A) or F508L (F) in 10 mM MgATP (green bars). (B–C, G–H) Closed (B, G) and open (C, H) dwell-time histograms (Sigworth and Sine, 1987) constructed from the events list of the records in (A, F); lower binning limit is 12 ms. Solid red lines are maximum likelihood fits of the dwell-times by a double- and a single-exponential distribution, respectively, with time constants (τ(1, 2)) and fractional amplitudes (a1, a2) printed in the panels. Dotted black lines in panels (B, G) depict the two components of the fit; vertical blue line marks the burst delimiter (tcrit) calculated using the method of (Magleby and Pallotta, 1983). (D–E, I–J) Dwell-time histograms of reconstructed interburst (D, I) and burst (E, J) events following suppression of closed events shorter than tcrit. Solid red lines in (D, I) replot the longer component of the double-exponential fits in (B, G). Solid red lines in (E, J) are maximum likelihood fits of the burst durations by single-exponential distributions (τ, time constant). Image published in: Sorum B et al. (2017) © 2017, Sorum et al. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution license Larger Image Printer Friendly View

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