Pharmacological influence of specific bradycardic agents on the pacemaker current of sheep cardiac Purkinje fibres. A comparison between three different molecules.

The diastolic depolarization rate of isolated sheep Purkinje fibres was reduced in the presence of micromolar concentrations of the 'specific bradycardic agent' falipamil (AQ-A39) and its congener UL-FS49. Both drugs reduced the amount of pacemaker current, if, activated during the diastolic depolarization phase. The if activation curve was reduced in amplitude but not shifted. UL-FS49 was more effective compared to falipamil in causing this reduction of if amplitude at similar concentrations. The reduction of the if amplitude was presumably caused by a drug-induced decrease in if current conductance. This if current block showed use-dependence. With UL-FS49 less and less if was activated with every successive voltage clamp pulse of a train, with little recovery of if block after a rest interval. Use-dependent block was smaller with comparable falipamil concentrations but full recovery was observed after a rest interval. No use-dependent block was observed with alinidine, a drug which also causes reduction of if by shifting its activation range to more negative potentials. These results indicate that the reduction of pacemaker current observed with two different types of 'specific bradycardic agents' is obtained by different mechanisms.