Gentamicin causes the fast depression of action potential and contraction in cultured cardiocytes

The short-term cardiotoxic effects of gentamicin were studied on electrical and mechanical activities in cultures of ventricular confluent cardiocytes of rats. Application of gentamicin to the bath lowered the spontaneous action potential firing rate which was restored when the external calcium was elevated. Fast local application and withdrawal of drugs to non-pacemaker cells allowed effect/dose curves to be made. Such application of 200 nmol gentamicin (approximated concentration: 0.8 x 10(-3)-8.0 x 10(-3) M) lowered the contraction amplitude by 50% and the action potential overshoot by 20% while the action potential duration and maximum diastolic potential remained unchanged. Gentamicin withdrawal was followed by a rapid (half time = 5 s) and complete restoration of contraction. Verapamil, Mn2+, EDTA and La3+ also diminished contraction and overshoot but their effects were reversed 28, 25, 6 and 1.5 times more slowly, respectively. Gentamicin, like La3+, could act extracellularly, probably by competing with calcium ions for some external membrane site.