Flecainide 1 mM blocked both currents completely. A continuous plot of Ica,L amplitude during an experiment with flecainide 1 mM is shown in Figure 2A (data from a different cell from that of Figure 1C). After six control pulses, the superfusate was rapidly exchanged with flecainide 1 mM, and within a further five pulses (5 s after application of the drug), Ica,L was completely blocked. Even with this large dose of flecainide, Ica,L recovered completely within 17 s of switching the superfusate back to normal Tyro-de’s solution (Figure 2A, inset). Figure 2B shows a plot of the mean time course of block of Ica,L by flecainide 1 mM during continuous pulsing (n=4).For each cell, the mean Ica,L amplitude of five control pulses was taken as the control value, and the amplitude of Ica,L elicited by each pulse in the presence of flecainide was expressed as a proportion of the control amplitude. The decline of Ica,L with flecainide 1 mM during continuous pulsing could be described by a single exponential process with a time constant of 0.81±0.02 s, and full block occurred within six pulses.
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Figure 2 Time course offlecainide block ofL-type calcium current (Ica,b)- A Main figure shows continuous measurements ofIca,L amplitude in normal Tyrode’s solution after rapidly switching the superfusate toflecainide 1 mMand on washout. Inset shows individual current records correlating to pulses 4, 12 and 29 in each of the three phases of the experiment. Block by flecainide 1 mM was rapid and reversible. B Mean time course ofIca,L block for four cells during continuous pulsing. The amplitude ofIca,L with each consecutive test pulse after adding 1 mM flecainide is expressed as a proportion of the control amplitude (relative current). The decline of the current following flecainide administration could be described by a single exponential function with a time course of 0.81 s