Use- and frequency-dependent blockade by UL-FS 49 of the if pacemaker current in sheep cardiac Purkinje fibres.
The mechanism by which the bradycardiac agent UL-FS 49 blocks the if pacemaker current was investigated in sheep Purkinje fibres using the two microelectrode voltage-clamp technique. If was activated by 1 s pulses applied between -30 mV and -120 mV at 0.4 Hz in a modified Tyrode solution containing BaCl2 and MnCl2, and with TRIS replacing most of the Na+. UL-FS 49 caused an exponential decline of the if current amplitude during a train of pulses. Both the rate and extent of the if 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.
Van Bogaert
P P
PP
Department of Physiology, University of Antwerp (RUCA), Belgium.
Goethals
M
M
Simoens
C
C
D000818:Animals; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D001552:Benzazepines / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006321:Heart / Q000294:innervation* / Q000502:physiology; D066298:In Vitro Techniques; D015636:Magnesium Chloride / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D011690:Purkinje Fibers / Q000187:drug effects*; D012756:Sheep
D017609:Barium Compounds; D001552:Benzazepines; D002317:Cardiovascular Agents; D002712:Chlorides; D015636:Magnesium Chloride; C024986:barium chloride; D001464:Barium; C043636:zatebradine