Effects of the antiarrhythmic agent EGIS-7229 (S 21407) on calcium and potassium currents in canine ventricular cardiomyocytes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-06

AUTHORS

János Magyar, Tamás Bányász, László Fülöp, Norbert Szentandrássy, Ágnes Körtvély, Anikó Kovács, Gábor Szénási, Péter P. Nánási

ABSTRACT

. Based on earlier pharmacological studies performed using conventional microelectrodes EGIS-7229 (S 21407), the novel antiarrhythmic candidate, was suggested to have a combined mode of action in cardiac tissues isolated from various mammalian species. In order to characterize the electrophysiological effects of the compound, its effects on calcium and potassium currents of isolated canine ventricular cardiomyocytes were studied in the present work using the whole cell configuration of the patch clamp technique. L-type Ca current (ICa) was significantly depressed by EGIS-7229 at concentrations of 3 µM or higher with no concomitant changes in the voltage-dependence of activation and time course of inactivation of ICa. The drug reversibly suppressed the rapid component of the delayed rectifier K current (IKr) in a concentration-dependent manner, having a K0.5 value of 1.1±0.1 µM and a slope factor of close to unity (1.23±0.16), indicating that probably one single binding site of high affinity may be involved in binding of EGIS-7229 to the IKr channel. In contrast, no changes in the slow component of the delayed rectifier K current (IKs) was observed with the compound up to the concentration of 100 µM, even if the current was fully activated by 8-bromo-cAMP. At a concentration of 10 µM or higher, EGIS-7229 caused also a moderate but significant reduction in the inward rectifier K current (IK1) and the transient outward K current (Ito) with no change in the voltage-dependence of activation and steady-state inactivation of Ito. Present results indicate that EGIS-7229 can be considered as a selective IKr blocker at low (1 µM) concentration; however, its combined (class III + IV) mechanism of action is evident at concentrations of 3 µM or higher. Suppression of ICa may explain the lack of development of early afterdepolarizations in the presence of EGIS-7229, predicting a relatively safe clinical application in contrast to pure class III compounds. More... »

PAGES

604-611

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s002100100409

DOI

http://dx.doi.org/10.1007/s002100100409

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049177907

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11414655


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