Triamterene inhibits the delayed rectifier potassium current (IK) in guinea pig ventricular myocytes.

Abstract

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 the slow component of IK (IE) was decreased 36±6% (n=6) and 51±8% (n=6) by triamterene 10-5 and 10`mol/L, respectively. After low-voltage short pulses (-20 mV; 250 milliseconds), tail current amplitude corresponding essentially to the rapid component of IK ('Kr) was decreased only 14±11% (n=9) and 19+10% (n=10) by triamterene 10-5 and 10-4 mol/L, respectively. These results were confirmed under conditions of pure IKS (block of IK, by E-4031) and pure IKr (block of Isi with nisoldipine, extracellular Ca 2+ decreased to virtually 0 mmol/L, and 250-millisecond depolarizing pulse to -20 mV). In contrast, triamterene had no effects on time-independent currents. Thus, data obtained indicate that triamterene, at clinically relevant concentrations, inhibits IKS in a selective manner, although both components of IK (IKr and IKS) were decreased. This block of 'K may explain triamterene-related prolongation of cardiac repolarization and warn about potential drug interaction with action potential-prolonging agents.

Dynamic Ca 2+ -Induced Inward Rectification of K + Current During the Ventricular Action Potential

“…Nifedipine and nisoldipine were applied at concentrations of 5 and 0.2 mol/L, respectively, both sufficient to achieve almost complete blockade of I CaL , 17 as also verified in the setting of the present study (data not shown). The effect of inhibiting Ca 2ϩ influx was also tested by lowering extracellular Ca 2ϩ concentration from 2 to 0.5 mmol/L (low Ca 2ϩ solution) and replacing it with Mg 2ϩ (see "Materials and Methods").…”

Impairment of Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Function by the Intravenous General Anesthetic Propofol

“…Our data both confirm the original observations and, more importantly, expand on them with respect to the addition of the QT interval analysis. The fact that propofol at concentrations less than 10 M had no significant effect on the QT C indicates that the observed slowing was not due to propofol-mediated inhibition of the cardiac I Ks current, which would prolong QT C because of delayed repolarization (Daleau and Turgeon, 1994), consistent with previous reports of a much lower sensitivity of I Ks channels to propofol (IC 50 of 250 M) (Heath and Terrar, 1997). Thus, the slowing of sinus rate observed both by us and others with low micromolar concentrations of propofol is probably due to propofol impairment of HCN channel function.…”

Lengthening of Cardiac Repolarization in Isolated Guinea Pigs Hearts by Sequential or Concomitant Administration of Two IKr Blockers

“…), 8,9,[15][16][17][18][19][20] prolong action potential duration by selectively blocking I Kr , whereas other drugs, such as indapamide or triamterene, block preferentially I Ks . 21,22 Drug-induced LQTS is often observed under conditions of impaired drug elimination as it was first described for the drug-drug interaction between the histamine H1-antagonist terfenadine and the macrolide antibiotic erythromycin. 23 Indeed, these events were explained mostly through an inhibition of terfenadine CYP3A-mediated metabolism by erythromycin (CYP3A inhibitor).…”