Effects of norfluoxetine on the action potential and transmembrane ion currents in canine ventricular cardiomyocytes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-08-26

AUTHORS

János Magyar, Norbert Szentandrássy, Tamás Bányász, Valéria Kecskeméti, Péter P. Nánási

ABSTRACT

Norfluoxetine is the most important active metabolite of the widely used antidepressant compound fluoxetine. Although the cellular electrophysiological actions of fluoxetine are well characterized in cardiac cells, little is known about the effects of its metabolite. In this study, therefore, the effects of norfluoxetine on action potential (AP) configuration and transmembrane ion currents were studied in isolated canine cardiomyocytes using the whole cell configuration of patch clamp techniques. Micromolar concentrations of norfluoxetine (1–10 μM) modified AP configuration: amplitude and duration of the AP and maximum velocity of depolarization were decreased in addition to depression of the plateau and elimination of the incisura of AP. Voltage clamp experiments revealed a concentration-dependent suppression of both L-type Ca2+ current, ICa (EC50=1.13±0.08 μM) and transient outward K+ current, Ito (EC50=1.19±0.17 μM) having Hill coefficients close to unity. The midpoint potential of the steady-state inactivation of ICa was shifted from −20.9±0.75 mV to −27.7±1.35 mV by 3 μM norfluoxetine (P<0.05, n=7). No such shift in the steady-state inactivation curve was observed in the case of Ito. Similarly, norfluoxetine caused no change in the steady-state current–voltage relationship of the membrane or in the density of the inward rectifier K+ current, IK1. All these effects of norfluoxetine developed rapidly and were fully reversible. Comparing present results with those obtained previously with fluoxetine, it can be concluded that norfluoxetine displays stronger suppression of cardiac ion channels than fluoxetine. Consequently, the majority of the cardiac side effects observed during fluoxetine treatment are likely to be attributed to its metabolite norfluoxetine. More... »

PAGES

203-210

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00210-004-0954-1

DOI

http://dx.doi.org/10.1007/s00210-004-0954-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017401459

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15338108


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