Effects of bekanamycin and dibekacin on the electrical activity of cardiac pacemaker cells

In spontaneously beating sinus venosus of the frog Caudiverbera caudiverbera the effects of bekanamycin and dibekacin, two aminoglycoside antibiotics, on action potentials of cardiac primary pacemaker cells were studied by intracellular recording. Bekanamycin and dibekacin induced a concentration-dependent decrease of the amplitude, overshoot and the rate of rise of the action potential. Both also flattened the slow diastolic depolarization leading to a marked decrease in beat rate. At the highest concentration used (1 x 10(-3) M), the aminoglycosides produced a complete inhibition of primary cells action potentials. It was preceded by the appearance of subthreshold oscillations of the membrane potential which were observed for a few minutes until the electrical activity of pacemaker cell ceased. During absence of impulse initiation a stable membrane potential about -40 mV was observed. Aminoglycoside effects, excepting those on SCL, were completely suppressed when external calcium was increased to 3.6 mM. The results support the conclusion that bekanamycin and dibekacin depress the electrical activity of pacemaker cells. It is suggested that this effect is induced by aminoglycosides blockade of the slow calcium current involved in both upstroke and slow diastolic depolarization and through modification of potassium outward current. Bekanamycin at a lower concentration than that needed to induce electrophysiological effects potentiated verapamil 1 x 10(-8) effects on cardiac pacemaker cells.