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 M) decreased the pacemaker current by a dual action. The voltage dependence ofi _f activation was shifted in the hyperpolarizing direction by 7.8±0.6 mV (n=18,p<0.001) and the conductance of the fully activated current was reduced to 73±2% (n=18,p<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 thei _f activation range. (3) Some prolongation of the action potential duration was observed at 28 M 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 currenti _x. (4) The action of alinidine oni _f 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.