Alinidine modifies the pacemaker current in sheep Purkinje fibers

(1) The "specific bradycardic agent" alinidine reduces the slope of the diastolic depolarization in sinoatrial tissue and Purkinje fibers. In short Purkinje fibers of sheep, alinidine (28 microM) decreased the pacemaker current by a dual action. The voltage dependence of if activation was shifted in the hyperpolarizing direction by 7.8 +/- 0.6 mV (n = 18, p less than 0.001) and the conductance of the fully activated if current was reduced to 73 +/- 2% (n = 18, p less than 0.001) of its control value. These effects were reversible and dose-dependent. (2) Ionophoretic injections of alinidine caused reversible reductions of the diastolic depolarization rate and simultaneous transient hyperpolarizing shifts of the if activation range. (3) Some prolongation of the action potential duration was observed at 28 microM and more pronounced at higher concentration. This was presumably the consequence of a reduction by alinidine of outward repolarizing current carried by the background inward rectifier and plateau current ix. (4) The action of alinidine on if resulted in a slower activation of a reduced fraction of the pacemaker current at the maximal diastolic potential level. This explains the decrease of the diastolic depolarization rate observed in Purkinje fibers.