Cardiac membrane currents as affected by an neuroleptic agent: droperidol.

Abstract

1. In frog atria, the effect of Droperidol (5×10−5 M/l) on action potential and membrane currents was tested using the sucrose-gap technique. 2. Droperidol caused a progressive reduction of height, rate of rise, and duration of the action potential without much affecting the shape of the falling phase. The action potential could not be restored by anodal polarization. The refractory period was drastically prolonged (after an initial shortening). The resting potential was almost unchanged. 3. Voltage clamp measurements revealed a strong suppression of peak transient (Na) inward current without any marked change in slow outward current. The time to peak transient current remained practically constant whereas the decline of Na current was considerably slowed. Restoration of Na current upon repolarization was significantly delayed (after a transient acceleration). 4. The curve relating steady-state availability of Na current to membrane potential was strongly depressed and slightly shifted to more negative potentials. 5. 42K flux measurements in resting atria failed to show any significant change in either efflux or influx. 6. The experimental data suggest an almost selective inhibition of the Na-carrying system based on i) a partial block of Na channels (reduction of\(\overline {g_{{\text{Na}}} } \) in the Hodgkin-Huxley terminology) and ii) an alteration of the Na inactivation-reactivation mechanism (delayed kinetics of the variable h). 7. Both effects account for an antifibrillatory action of Droperidol: When the membrane repolarizes from a spike potential, the Na current available at any given moment is reduced both absolutely and relatively, and the state of refractoriness is prolonged.