Mechanisms of action of beta-adrenergic agents on the arrhythmogenic transient inward current in rabbit Purkinje fibers

Xinqiang Han, Gregory R. Ferrier

Résultat de recherche: Articleexamen par les pairs

6 Citations (Scopus)

Résumé

Catecholamines increase the amplitudes of oscillatory afterpotentials (OAP) and peak magnitude of the transient inward current (Iti) responsible for OAP. The objectives of this study were to determine whether β-adrenoceptor stimulation can induce Iti, and to determine the mechanism by which β-adrenoceptor stimulation increases the magnitude of Iti. Experiments were performed using standard two electrode voltage-clamp techniques in isolated rabbit Purkinje fibers. Holding potential was either -50 or -80 mV. The Iti was elicited by repolarizing steps, following 1.5 or 3 s activating steps to potentials near 0 mV. Isoproterenol (ISO) failed to induce the Iti at concentrations from 10-8 to 10-6 m. However, ISO (10-7 m) significantly increased peak magnitude of spontaneously occurring Iti (P < 0.05), or Iti induced by acetylstrophanthidin (AS) (P < 0.05). ISO also shifted the minimum activation voltage 10 mV more negative (P < 0.05). The currentvoltage relationship demonstrated that ISO significantly increased the range of potentials over which Iti≥5 nA occurred, but did not significantly shift the voltage at which maximum peak current was observed. Effects of ISO on Iti were blocked by 10-7m propranolol or atenolol. Mn2+ (2 mm) or verapamil (2 μm) blocked the slow inward current (Isi) more than 80% before substantially decreasing peak Iti. Either agent blocked stimulation of Isi but not Iti by ISO at 10-7m. In contrast, quinacrine (20 μm), an inhibitor of Na+Ca2+ exchange, abolished stimulation of Iti by ISO while having no significant effect on Isi. Our results indicate that β-adrenoceptor stimulation cannot induce Iti in rabbit Purkinje fibers, but can enhance the Iti induced by other means, by stimulating Na+Ca2+ exchange.

Langue d'origineEnglish
Pages (de-à)551-562
Nombre de pages12
JournalJournal of Molecular and Cellular Cardiology
Volume23
Numéro de publication5
DOI
Statut de publicationPublished - mai 1991

Note bibliographique

Funding Information:
Please address all correspondence and reprint requests to: Gregory R. Ferrier, Department of Pharmacology, Charles Tupper medical building, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7 This study was supported in part by a grant from the Medical Research Council of Canada. X. Han is fellow of the Medical Research Council of Canada

ASJC Scopus Subject Areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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