Membrane actions of quinidine sulfate in the rabbit atrioventricular node studied by voltage clamp method

The effects of quinidine (0.01-20 micrograms/ml) on spontaneous action potentials and membrane current systems of the rabbit atrioventricular node were studied. At therapeutic concentrations, this drug decreased the action potential amplitude, the maximal diastolic potential, the threshold potential as well as the maximal rate of depolarization and showed a negative chronotropic action. Quinidine, at 5 micrograms/ml, decreased the peak slow inward current by 30.2%, increased its time constant of inactivation by 27.3%, shifted the steady-state inactivation curve toward more negative membrane potentials by 2.8 mV and decreased its fully activated current. Quinidine exerted not only resting but also use-dependent blocking actions on the slow inward current. The depression of the action potential upstroke can thus be explained by the reduction in this current. The outward K+ tail current was decreased by 65.4% and its deactivation time constant was increased by 19.0%. These effects may have contributed to the prolongation of the action potential duration, the reduction in the maximal diastolic potential and the slowing of diastolic depolarization. Quinidine shifted the steady-state activation curve for this K+ current toward hyperpolarization by as much as 7.8 mV. It decreased the hyperpolarization-activated inward current by 16.3% and increased its activation time constant by 10.1%, but this current appeared to play a small role in reducing the rate of diastolic depolarization. These observations indicate that, depending upon dose, quinidine has the potential to decrease all of the time- and voltage-dependent ionic currents in atrioventricular nodal cells.