The blocking action of tedisamil on Iso was studied in more detail by calculating the fractional block as it developed during the first 100 ms of the test step to +50 mV. Figure 6A shows the monoexponential time course of fractional block development as well as the computer-generated monoexponential curves fitted to the data points. Assuming a simple reversible interaction of one tedisamil molecule with one ion channel, the time constants of the onset of block (Ton) at the various concentrations investigated were used to construct a plot of the linear function:
where k1 and k2 are the association and dissociation rate constants, respectively, and [Tedisamil] is the concentration of tedisamil in pM. The apparent dissociation constant Kd can be calculated from the ratio of k2/ki, and amounted to 2.6 pM. This value corresponds well with the IC50 value obtained from the concentration response curve shown in Figure 5.
Figure 5 Concentration-response curves for the effects oftedisamil on peak transient outward current (Ito) amplitude and sustained outward current (Iso) amplitude at the end of the test pulse (300 ms) in human atrial myocytes. Ordinate: normalized current (current value in the presence ofdrug [T]) was subtracted from current under control conditions (C) and normalized to the control value, ie, (C-T)/C. Values are mean ± SEM, n=3 to 8. In each cell only a single concentration was tested Looking for a great online pharmacy you could trust and where you could find Generic Cialis Professional cialis professional at best prices? You have one pharmacy like that already and can finally enjoy the best quality of service ever experienced.