Effects of the antiarrhythmic agent tedisamil on cardiac potassium currents in humans (part 9). RESULTS

26 Aug
2012

RESULTS

The effect of tedisamil 10 |J.M on total outward current was use-dependent. After 2 mins of rest at -80 mV, reduction of peak current developed more quickly when clamp steps to +60 mV (duration 300 ms) were applied with a frequency of 1 Hz than one of 0.2 Hz; Ton values were 0.7 s and 3.7 s, respectively (Figure 7A). After a steady state of block had been obtained with a train of 10 pulses to +60 mV (duration 300 ms) at 1 Hz, recovery from block was tested with the same clamp step after intervals of 0.5 to 60 s duration at -80 mV. Total outward current recovered completely from tedisamil block after 30 s at a potential of -80 mV (Figure 7B); on average, the recovery time constant was 7.9±1.6 s (n=3).

Effects of the antiarrhythmic agent tedisamil on cardiac potassium currents in humans

Figure 6 Kinetic analysis oftedisamil-induced block of sustained outward current (Iso) in human atrial myocytes. A Development of fractional block ([control – drug] / control) during the first 100 ms of a steady state test step to +50 mV for 1, 2, 5 and 10 fiM of tedisamil. The time constants, ron, were 53.5±18.6 ms (n=4)for 1 juM, 30.7 ms (n=2)for 2 juM, 10.6±1.1 ms (n=3) for 5 juM and 10.9±3.6 ms (n=5)for 10juM of tedisamil. B Calculation of rate constants from the linear regression (B) of the plot of1/Ton versus the concentration of tedisamil in micromoles according to the formula (1/ton = kj x [tedisamil] + k2), where kj and k2 are association and dissociation rate constants, respectively. From the regression line k1 was 8.4×106/M/s, and k2 was 22.1/s. The apparent dissociation constant, Kd, was calculated to be 2.6juM, which agrees with the experimentally measured concentration of half maximum block
Effects of the antiarrhythmic agent tedisamil on cardiac potassium currents in humans

Figure 7 Onset oftedisamil-induced block on peak outward current (M) and recovery from block in human atrial myocytes (tedisamil 10 uM). A After 2 mins’ rest at-80 mV, clamp steps to +60 mV were applied at a frequency of 0.2 Hz (circles) or 1 Hz(squares). Open symbols, control; filled symbols, in the presence of tedisamil 10 uM. B Recovery of total outward current from tedisamil block. т Time constant  Most advantageous shopping with best pharmacy you can choose in just a second: buy ortho tri-cyclen online best price and find out exactly how little it could cost you to be getting your medications quick and easy.

top