A Novel and Lethal De Novo LQT-3 Mutation in a Newborn with Distinct Molecular Pharmacology and Therapeutic Response
Figure 4
The F1473C mutation has multiple biophysical consequences.
A. The F1473C mutation causes an 8.8±1.6 mV depolarizing shift in the steady state availability curve. Data shown for WT (n = 9, open triangles) and F1473C (filled squares, n = 25) channels. B. Mutation at F1473C speeds the time course of recovery from inactivation as measured at −100 mV following a 50 ms pulse to −10 mV. WT (open triangles, n = 5) and F1473C (closed squares, n = 5). C. Normalized WT (grey) and F1473C (black) currents in response to a ramp in voltage from −120 mV to +40 mV (see Methods S1) over the course of 1s reveal F1473C-enchanced inward current over a broad range of voltage. Shown are averaged TTX-sensitive currents for WT (light grey, n = 4) and F1473C (black, n = 11) channels. Note the inverted bell-shaped response of WT channels to this protocol reveals “window” of current for WT channels (see text for details).