**Under the experimental conditions** of this study, therefore, flecainide inhibited AVN Ica,L rapidly and reversibly. It is also evident from Figure 1A,B,c that flecainide reduced Ica,L in a dose-dependent fashion. An additional (and qualitative) observation was that Ica,L and INa appeared to show differential sensitivities to the drug. This is shown most clearly in Figure 1B – flecainide 100 ^M almost completely abolished INa in this cell, while reducing Ica,L only partially.

Five different doses of flecainide ranging from 10 ^M to 1 mM were applied to +10 mV by using the two-step protocol to elicit Ica,L. Figure 3A shows the mean fractional Ica,L inhibition plotted against drug concentration (on a logarithmic scale). From the data points alone, half-maximal inhibition of Ica,L by flecainide is predicted to occur in the range between 50 ^M and 100 ^M. To obtain a value for Kd for Ica,L block, the data were fitted with the Langmuir function given by equation 1 (Methods). The data were fitted by using a Kd of 63.4±8.2 ^M and a Hill coefficient of 1.3.

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*Figure 3 A Dose-response relation for L-type calcium current (Ica,L) block by flecainide. Vertical axis represents ‘fractional block’ of Icci,l by flecainide (1.0 = total block; 0= no block), and the horizontal axis shows flecainide concentration plotted on a logarithmic scale. Five doses offlecainide between 10 цM and 1 mM were applied (numbers in brackets represent number of cells exposed to each dose). Data were fitted by equation 1 in the Methods section with Kd 63.4 ^M and Hill coefficient 1.3. B,C Voltage-dependent effects offlecainide on Ica,L. B Current-voltage relation for Ica,L in normal Tyrode’s solution and after application offlecainide 100 ^M (inset shows voltage protocol) by using 10 mV steps to test potentials between -40 and +40 mV). Curve-fits to current-voltage relations were obtained using equation , described in the Methods. C Degree of Ica,L block (vertical axis) plotted against test potential (horizontal axis; same cell as B). IFlec Flecainide current; Icontrol Control current*