Effects of (+)- and (±)-sotalol on repolarizing outward currents and pacemaker current in sheep cardiac Purkinje fibres View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1989-12

AUTHORS

F. Berger, U. Borchard, D. Hafner

ABSTRACT

This study was aimed to differentiate the action of (+)- and (±)-sotalol (10–1000 μmol/l) on membrane currents which are active during the repolarization of cardiac action potentials Effects where studied in shortened sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique Action potentials were activated at a frequency of 0.25 Hz and membrane currents at 0.03 Hz or 0.05 Hz in most experiments.Out of the currents investigated the transient outward current (ito) reacted most sensitively to (+)- and (±)-sotalol. Ito-amplitude was decreased on the average to 77% of reference at 10 μmol/l and to 53% at 1000 μmol/l (+)- or (±)-sotalol. The maximally available ito-current was decreased but the voltage-dependent control of inactivation was left nearly unchanged. The initial inwardly rectifying current (iKi), which propels the last repolarization phase of the action potential and controls resting potential to a large extent was reduced on the average to 93% of reference at 10 μmol/l and to 62% at 1000 μmol/l (+)- or (±)-sotalol. Time-dependent (delayed) outward current (iK) was on the average not affected by (+)- or (±)-sotalol up to 100 μmol/l and was decreased to 84% of reference current under the influence of 1000 μmol/l. An initial outward current, which is activated at positive membrane potentials (iinst) was not clearly affected by (+)- or (±)-sotalol at concentrations up to 1000 μmol/l Pacemaker current (if) was not influenced by the drugs up to 100 μmol/l. Only at 1000 μmol/l was the amount of available if-current decreased to 79% of reference. (The potential-dependent control of activation was not affected) Time constants of time-dependent currents ito, iK and if did not change in concentrations up to 1000 μmol/l of the drug.Action potential duration increased at (+)- or (±)-sotalol concentrations ≥ 10 μmol/l and maximal prolongation was achieved at concentrations of 100–300 μmol/l Resting potential remained nearly unchanged at these concentrations, but the membranes depolarized at 1000 μmol/l. According to our data action potential prolongation in sheep Purkinje fibres under the influence of (+)- and (±)-sotalol correlates to the drug-induced block to ito-current and inwardly rectifying iK1-current. More... »

PAGES

696-704

References to SciGraph publications

  • 1976-06. Cardiac Purkinje fibers: Cesium as a tool to block inward rectifying potassium currents in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1964-03. Voltage clamp technique in mammalian cardiac fibres in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1982-02. Existence of two transient outward currents in sheep cardiac Purkinje fibers in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1983-02. α2-adrenoceptors in rat resistance vessels in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 1977-02. Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1987-12. The mechanism of the inactivation of the inward-rectifying K current during hyperpolarizing steps in guinea-pig ventricular myocytes in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1984-12. Barium-induced blockade of the inward rectifier in calf Purkinje fibres in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1983-06. The shortening of the action potential by DNP in guinea-pig ventricular myocytes is mediated by an increase of a time-independent K conductance in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 1980-12. Cow ventricular muscle in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/bf00717747

    DOI

    http://dx.doi.org/10.1007/bf00717747

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031922050

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/2615859


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