Tedisamil 10 |JM affected Ito in human atrial and subepicardial ventricular myocytes by reducing peak amplitude and increasing rate of inactivation (Figure 4A,B). The average time constant of apparent inactivation (Ti) of Ito and Iso in atrial and ventricular myocytes in both the presence and the absence of 10 |JM tedisamil is depicted in Figure 4C and D. Ti of atrial Ito was least affected. To quantify the block for the concentration response curves in Figure 5, the drug effects on peak current amplitude of Ito were compared with those on late current amplitude of Iso after normalization of the effects to the respective current amplitudes under control conditions. The blocking effects of tedisamil on the two current amplitudes apparently saturate between 5 and 10 |JM at about 50% of the respective control values. From this presentation, Iso appeared to be somewhat more sensitive than Ito to tedisamil. IC50 values were in the range of 1 to 3 |JM. 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 4 Effects of tedisamil on transient outward current (Ito) in human atrial and ventricular myocytes. A,B Current tracings with clamp steps from -80 mV to +60 mV before (C) and 5 mins after addition of tedisamil (T, 10 fiM). For atrial myocytes (A), Ito was taken as the difference between total current and sustained outward current (Iso) (Figure 2C);for ventricular myocytes, Ito was the total outward current. Time constants of inactivation (Ti) at +60 mV for Ito and Iso in atrial myocytes (C) and for Ito in ventricular myocytes (D), before (Control) and 5 mins after exposure to tedisamil (10 fiM). Values are mean ± SEM Most reliable pharmacy offering efficient medications like Sale Cialis Professional cialis professional is ready to offer its services and all the help you need. Your health is precious, and so are you: as customer, person and patient, no matter which kind of treatment you are looking for.