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

Eur J Pharmacol. 1990 Oct 9;187(2):241-56. doi: 10.1016/0014-2999(90)90011-t.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Barium / pharmacology
  • Barium Compounds*
  • Benzazepines / pharmacology*
  • Cardiovascular Agents / pharmacology*
  • Chlorides*
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Heart / innervation*
  • Heart / physiology
  • In Vitro Techniques
  • Magnesium Chloride / pharmacology
  • Membrane Potentials / drug effects
  • Microelectrodes
  • Purkinje Fibers / drug effects*
  • Sheep

Substances

  • Barium Compounds
  • Benzazepines
  • Cardiovascular Agents
  • Chlorides
  • Magnesium Chloride
  • barium chloride
  • Barium
  • zatebradine