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. Author manuscript; available in PMC: 2009 Dec 1.
Published in final edited form as: Circ Arrhythm Electrophysiol. 2008 Dec 2;1(5):370–378. doi: 10.1161/CIRCEP.108.788349

Figure 6.

Figure 6

Effects of mexiletine on WT and G1631D. (A) Mexiletine (100 µM) block of WT (n=8) and G1631D (n=8) during a 1Hz train of depolarizing pulses to −10mV from a holding potential of −120mV. (B) Tonic mexiletine block of WT and G1631D. Upper traces (left, middle) illustrate the effects of 100µM mexiletine during a single depolarizing voltage step to −10mV. Normalized traces (right) recorded in the absence (control) or presence of drug illustrate the effect of mexiletine on the inactivation time course. The plot illustrates the concentration-response relationships for tonic block by mexiletine (each data point represents the mean of 4–12 cells). (C) Use-dependent mexiletine block of WT and G1631D. Upper traces (left, middle) illustrate the steady state effects of 100µM mexiletine during a 1Hz pulse train. Normalized traces (right) recorded in the absence (control) or presence of drug (100th pulse) illustrate the effect of mexiletine on the inactivation time course. Time constants in the absence of drug were: τ1=7.7±0.7ms, τ2=19.7±0.6ms, n=8; and in the presence of 100µM mexiletine: τ1=4.5±0.7ms, τ2=10.9±1.0ms, n=8 (P=0.0095 for τ1; P<0.0001 for τ2). The plot illustrates the concentration-response relationships for use-dependent block by mexiletine (each data point represents the mean of 4–12 cells). The lines in B and C were fit to the data according to the Hill equation.