Abstract

The effect of alinidine on transmembrane electrical activity of nodal and atrial fibers was studied in the isolated right auricle of the guinea-pig. Alinidine was applied in concentrations between 0.72 and 28.5 X 10(-5) M. In nodal fibers the main effect was a dose-dependent decrease in rate of diastolic depolarization and a delayed repolarization of especially the terminal part of the action potential. In both fiber types alinidine causes a marked delay of the terminal part of repolarization; the increase of the duration of the action potential was related to the alinidine concentration over the whole concentration range used. In addition the amplitude of the action potential and the maximal diastolic potential are increased dose dependently up to a concentration of 2.8 x 10(-5) M. Application of higher concentrations does not increase these parameters. In nodal fibers diastolic depolarization is already depressed considerably at a relatively low concentration. This is particularly so in fibers that normally have a high rate of diastolic depolarization, i.e., the dominant pacemaker fibers. A shifting of the pacemaker seems only to occur at high concentrations (11.4 X 10(-5) M or higher). The strong negative chronotropic effect of alinidine can be attributed to both the depression of diastolic depolarization and the increase in duration of the action potential. At low concentrations the increase of the maximum diastolic potential can also contribute to the slowing of the heart rate.