Triamterene inhibits the delayed rectifier potassium current (IK) in guinea pig ventricular myocytes.
In humans, proarrhythmia during therapy with action potential-prolonging drugs can be associated with hypokalemia often provoked by concomitant administration of diuretic agents. Consequently, therapy with class III antiarrhythmics and K(+)-sparing diuretics, such as triamterene, may be indicated. Triamterene, along with its K(+)-sparing properties, exhibits other pharmacological effects. In the heart, it can increase action potential duration (guinea pig atria and papillary muscles), protect against reperfusion-induced arrhythmias (rat), and increase the QT interval (humans). Therefore, studies were undertaken to assess effects of triamterene on cardiac K+ repolarizing currents. Guinea pig ventricular myocytes were superfused at 30 degrees C with Cd(2+)-containing solution to block Isi and held at -40 mV to inactivate INa. Currents were measured in the whole-cell configuration of the patch-clamp technique. The delayed rectifier outward current (IK) was elicited by short (250-millisecond) and long (5000-millisecond) depolarizing pulses, and time-independent currents were assessed by a rapid ramp test protocol. After high-voltage long pulses (+50 mV; 5000 milliseconds), tail current amplitude of the slow component of IK (IKs) was decreased 36 +/- 6% (n = 6) and 51 +/- 8% (n = 6) by triamterene 10(-5) and 10(-4) mol/L, respectively. After low-voltage short pulses (-20 mV; 250 milliseconds), tail current amplitude corresponding essentially to the rapid component of IK (IKr) was decreased only 14 +/- 11% (n = 9) and 19 +/- 10% (n = 10) by triamterene 10(-5) and 10(-4) mol/L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
- Copyright © 1994 by American Heart Association