Because of its slow or absent inactivation, Iso resembles a delayed rectifier current. To test this hypothesis, the effect of the selective Ikt blocker almokalant (1 |J,M) on this current (Figure 3A) was investigated in a concentration that exceeds the concentration of half maximum block (IC50) for Ikt in rabbit ventricular myocytes by a factor of 20 ; however, the drug did not affect Iso. Tedisamil (10 |J.M) on the other hand accelerated the inactivation of Iso (Figure 3B). At +60 mV, the mean inactivation time constants, Ti, were 169±49 ms before and 23±5 ms after exposure to tedisamil (P<0.05, n=9). Despite large variations in inactivation time constant of Iso with clamp step duration of 300 ms under control conditions, similar effects were observed with 100 |J.M clofilium (Figure 3C).Ti values were 577±176 ms before and 63±21 ms after exposure to clofilium (P<0.05, n=4). The apparent acceleration of inactivation is compatible with an open channel block. The voltage dependence of the late current is depicted in Figure 3D to F. From the current-voltage curves it is evident that tedisamil and clofilium reduced the late current in the potential range between -10 and +60 mV, and that the block is state-dependent and not voltage-depend. A pharmacy you can fully trust is ready to offer best selection of cheap and effective medications that work the way they are expected to every time and are always available: you could buy discount Cialis Professional cialis professional and enjoy all the convenient services offered right now.
Figure 3 Effects of three antiarrhythmic drugs on sustained outward current (Iso) in human atrial myocytes. A-C Currents at +60 mV (for protocol see Figure 2B) before (Control) and after 5 to 10 mins of exposure to almokalant (1 fiM), tedisamil (10 fiM) and clofilium (100 fiM). Arrowheads indicate zero current level. D-F Current-voltage relations of late Iso before (Control) and after exposure to the individual agents. Current at the end of the 300 ms clamp step (Ilate) is expressed as current densities (pA/pF). Values are mean ± SEM. Im Membrane current; VM Membrane voltage.