Use- and frequency-dependent blockade by UL-FS 49 of the i f pacemaker current in sheep cardiac Purkinje fibres

Abstract

The mechanism by which the bradycardic agent UL-FS 49 blocks the i f pacemaker current was investigated in sheep Purkinje fibres using the two microelectrode voltage-clamp technique. I f was activated by 1 s pulses applied between −30 mV and −120 mV at 0.4 Hz in a modified Tyrode solution containing BaCl 2 and MnCl 2, and with TRIS replacing most of the Na +. UL-FS 49 caused an exponential decline of the i f current amplitude during a train of pulses. Both the rate and extent of the i f reduction increased with drug concentration, without there being a resting blockade. Recovery from blockade followed a single exponential time course during prolonged hyperpolarizations. The recovery rate was extremely slow and increased with more negative voltages, as did the extent of steady state recovery from blockade. A frequency-dependent reduction of the diastolic depolarization rate resulted from a use-dependent blockade of the pacemaker current.