Tomoyuki Furuse

Studies on the Bradycardia Induced by Aprindine in Rabbit Sinoatrial Node Cells

The effects of aprindine (1 X 10(-7) to 4 X 10(-6) M) were examined on membrane potential and current of rabbit sinoatrial node by means of conventional microelectrode and double microelectrode voltage clamp methods. Aprindine decreased, in a dose-dependent manner, the spontaneously firing frequency, the maximum rate of depolarization and the action potential amplitude, and prolonged the action potential duration at half-amplitude. The slope of the diastolic depolarization was also reduced by the drug. In the voltage clamp experiment, aprindine reduced the slow inward current (Isi), the time-dependent potassium current (Ik) and the hyperpolarization activated current (Ih). The recovery time constant of Isi was prolonged by aprindine, while the kinetics of Ik was not altered. It is indicated that aprindine does not have an effect on a specific conductance or a single current system, but that the drug exerts an inhibitory effect on the electrical activity of sinoatrial node.

Estimation of Catecholamine Potencies on the Myocardium by Means of a New Method

A simple method is described for evaluating the potencies of catecholamines on the slow response of myocardium. Catecholamines depolarize guinea pig ventricular muscle cells exposed to the high K+ (27 mmol/l) Tyrodes solution containing 0.2 mmol/l Ba through an increase in slow channel conductance. Higher concentrations of catecholamines in addition induce spontaneous action potentials. This model was used to estimate and compare catecholamine potencies on myocardium. Catecholamine concentrations needed for depolarization alone or for depolarization plus automatic activity were taken as basis for comparison. The order of potency obtained by means of this new method was: l-isoproterenol greater than l-adrenaline greater than or equal to dl-noradrenaline greater than or equal to dobutamine greater than or equal to dopamine. This is similar to the order reported with other methods.