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Fig. 3. LQT2 mutations in the putative CNBD of HERG prevent surface localization caused by ER retention. (A) PK analysis of natural mutations in the putative CNBD of HERG. Membranes were simultaneously probed with anti-HA and anti-CASK antibodies. Arrows indicate the CASK and the mature band of HERG (M) at their respective molecular weights. (B) Quantification of representative experiments described in A (n indicates the number of different experiments used for quantification). Histogram bars show PK insensitivity (black) or significant sensitivity (white, P<0.05). In all cases, the HA signals were normalized to the corresponding CASK signal. For HERG_R823K, the pixel intensities of both the immature and the mature bands were considered. (C) Quantification of tail-current density generated in cells expressing HERG_wt channel or the indicated mutants. Transfected cells were selected as described and subjected to depolarization steps. Currents were measured at –60 mV and normalized to individual cell capacitance. Black bars indicate mutants with similar activity to mock-transfected cells (Mock).

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