Effect of aprindine on transmembrane currents and contractile force in frog atria

The effects of aprindine on transmembrane currents in frog (Rana Ridibunda) atrial trabeculae were studied using a voltage clamp technique. Aprindine (1 x 10(-6) g/ml) reduced maximum inward sodium current by 38.6 +/- 7.2% (mean +/- S.E.M., n = 6), but had no effect on the slow inward current or outward current. A higher dose of aprindine (2.8 +/- 10(-5) g/ml) suppressed both the fast inward current and the slow inward current. Outward current was decreased at membrane potentials between -80 and -45 mV and increased at membrane potentials positive to -20 mV. In addition, aprindine was tested on frog (R. Ridibunda) atrial strips in which the transmembrane action potential and contractile force were recorded. The low dose of aprindine (1 x 10(-6) g/ml) depressed action potential amplitude and dV/dt and slightly increased action potential duration, but had no effect on contractile force. The higher dose (2.8 x 10(-5) g/ml) significantly reduced developed tension and dP/dt, decreased action potential amplitude and dV/dt and increased action potential duration. Aprindine (2.8 x 10(-5) g/ml) also depressed slow channel dependent membrane oscillations induced in atrial trabeculae by injection of current pulses. These data indicate that aprindine possesses fast and slow channel blocking properties, the latter being more apparent at high concentrations of the drug, and affects outward current differentially, depending on the membrane potential.