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Figure 1. CNGB3 disease-associated mutations impart a gain-of-function phenotype in heteromeric CNG channels. (A) Diagram showing CNGB3 subunit topology with approximate locations of disease associated mutations examined in this paper. (B) Representative current traces from inside-out patches excised from Xenopus oocytes expressing heteromeric human A3+B3 channels activated by a saturating concentration (1 mM) of cGMP in the presence (arrowhead) or absence of 25 μM L-cis-diltiazem. Current traces were elicited using voltage steps from a holding potential of 0 mV, to +80 mV, −80 mV, and then returning to 0 mV. (C) Box plots summarizing the sensitivity to diltiazem block of channels containing disease-associated mutations compared to wild type A3+B3 heteromeric (WT) and CNGA3-only homomeric channels (A3). Data are expressed as the ratio of the 1 mM cGMP current amplitude at +80 mV in the presence and absence of diltiazem (as in B). Boxes represent 25th–75th percentiles, lines show the median, and whiskers represent the 5th–95th percentiles. (D) Summary of current densities at 5 μM cGMP for CNGB3 disease-associated mutations. Current-density estimates are based on cGMP dose-response data and estimates of patch area using patch electrode resistance (Sakmann and Neher, 1995). Four of the five mutations examined had an increase in the 5 μM current density compared to wild type A3+B3 channels (p < 0.001, single-factor ANOVA, n = 6–23; Holm's t-test, **p < 0.01, ***p < 0.001). Image published in: Meighan PC et al. (2015) Copyright © 2015 Meighan, Peng and Varnum. 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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