EFFECTS OF POTASSIUM CHANNEL BLOCKERS ON THE ACTION-POTENTIALS AND CONTRACTILITY OF THE RAT RIGHT VENTRICLE

1. The effects of several potassium channel blockers on the action pot entials and contractile force of the electrically driven rat right ven tricle have been determined. 2. Glibenclamide, which blocks the ATP-se nsitive potassium channels, had no effect on the ventricular action po tentials or contractile force responses. 3. 4-Aminopyridine, which blo cks the Na+-activated potassium channels in ventricles, at 0.3-3 mM in creased the amplitude and prolonged the action potentials, and also au gmented the force responses to cardiac stimulation and to isoprenaline . 4. Clofilium, a selective blocker of the delayed outward rectifying potassium channel, at 0.1 and 0.3 mu M prolonged the action potentials . At 0.1 mu M, clofilium augmented the cardiac stimulation responses a nd, at 0.3 mu M, clofilium augmented the maximal responses to isoprena line. At 1 and 3 mu M, clofilium had a lesser ability to prolong actio n potentials and did not alter force responses. 5. Procaine blocks the Na+-activated and the delayed outward rectifying potassium channels a nd, at higher concentrations, sodium channels. Procaine, at 30 mu M, p rolonged the action potentials and augmented the force responses to is oprenaline, presumably by blocking potassium channels. Procaine, at 1 mM, had no effect on action potentials but reduced the maximal force r esponses to isoprenaline, probably by blocking sodium channels. 6. Tet raethylammonium blocks the inward rectifying and delayed outward recti fying potassium channels. Tetraethylammonium, at 1 and 3 mM, prolonged the action potentials and augmented all of the force responses; these effects are likely to be predominantly due to blocking the outward re ctifying potassium channel. Thus, in the presence of procaine, the eff ects of tetraethylammonium are predominantly due to the additional blo ckade of the inward rectifying potassium channel and there were no eff ects. 7. None of the potassium channel blockers at any of the concentr ations tested had arrhythmogenic effects alone or in the presence of i soprenaline. 8. In summary, this study has shown that blockade of the Na+-activated and the delayed outward rectifying, but not the ATP-sens itive or inward rectifying, potassium channel is associated with prolo ngation of the action potentials, augments the contractile force respo nses, and is not arrhythmogenic on the rat right ventricle. New drugs that block the Na+-activated or delayed outward rectifying potassium c hannel may have potential as positive inotropes in the treatment of he art failure.