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001-es BibID:	BIBFORM037322
035-os BibID:	WOS:000294414700011
Első szerző:	Szebeni Andrea
Cím:	Can the electrophysiological action of rosiglitazone explain its cardiac side effects? / A. Szebeni, N. Szentandrássy, P. Pacher, J. Simkó, P. P. Nánási, V. Kecskeméti
Dátum:	2011
ISSN:	0929-8673
Megjegyzések:	Recent large clinical trials found an association between the antidiabetic drug rosiglitazone therapy and increased risk of cardiovascular adverse events. The aim of this report is to elucidate the cardiac electrophysiological properties of rosiglitazone (R) on isolated rat and murine ventricular papillary muscle cells and canine ventricular myocytes using conventional microelectrode, whole cellvoltage clamp, and action potential (AP) voltage clamp techniques.In histidine-decarboxylase knockout mice as well as in their wild types R (1-30 ?M) shortened AP duration at 90% level of repolarization (APD90) and increased the AP amplitude (APA) in a concentration-dependent manner. In rat ventricular papillary muscle cells R (1-30?M) caused a significant reduction of APA and maximum velocity of depolarization (Vmax) which was accompanied by lengthening of APD90.In single canine ventricular myocytes at concentrations ?10 ?M R decreased the amplitude of phase-1 repolarization, the plateau potential and reduced Vmax. R suppressed several ion currents in a concentration-dependent manner under voltage clamp conditions. The EC50value for this inhibition was 25.2?2.7 ?M for the transient outward K+ current (Ito), 72.3?9.3 ?M for the rapid delayed rectifier K+ current (IKr), and 82.5?9.4 ?M for the L-type Ca2+ current (ICa) with Hill coefficients close to unity. The inward rectifier K+ current (IK1) was not affected by R up to concentrations of 100 ?M. Suppression of Ito, IKr, and ICa has been confirmed under action potential voltage clamp conditions as well.The observed alterations in the AP morphology and densities of ion currents may predict serious proarrhythmic risk in case of intoxicationwith R as a consequence of overdose or decreased elimination of the drug, particularly in patients having multiple cardiovascular risk factors, such as elderly diabetic patients.
Tárgyszavak:	Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban antidiabetic agents rosiglitazone action potential ion currents egyetemen (Magyarországon) készült közlemény
Megjelenés:	Current Medicinal Chemistry. - 18 : 24 (2011), p. 3720-3728. -
További szerzők:	Szentandrássy Norbert (1976-) (élettanász) Pacher Pál Simkó József (1974-) (belgyógyász, kardiológus) Nánási Péter Pál (1956-) (élettanász) Kecskeméti Valéria
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001-es BibID:	BIBFORM037321
Első szerző:	Szentandrássy Norbert (élettanász)
Cím:	Effects of rosiglitazone on the configuration of action potentials and ion currents in canine ventricular cells / Szentandrássy N., Harmati G., Bárándi L., Simkó J., Horváth B., Magyar J., Bányász T., Lőrincz I., Szebeni A., Kecskeméti V., Nánási P.P.
Dátum:	2011
ISSN:	0007-1188
Megjegyzések:	BACKGROUND AND PURPOSEIn spite of its widespread clinical application, there is little information on the cellular cardiac effects of the antidiabetic drug rosiglitazone in larger experimental animals. In the present study therefore concentration-dependent effects of rosiglitazone on action potential morphology and the underlying ion currents were studied in dog hearts.EXPERIMENTAL APPROACHStandard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts.KEY RESULTSAt concentrations ?10 mM rosiglitazone decreased the amplitude of phase-1 repolarization, reduced the maximum velocity of depolarization and caused depression of the plateau potential. These effects developed rapidly and were readily reversible upon washout. Rosiglitazone suppressed several transmembrane ion currents, oncentration-dependently, under conventional voltageclamp conditions and altered their kinetic properties. The EC50 value for this inhibition was 25.2 ? 2.7 mM for the transient outward K+ current (Ito), 72.3 ? 9.3 mM for the rapid delayed rectifier K+ current (IKr) and 82.5 ? 9.4 mM for the L-type Ca2+ current (ICa) with Hill coefficients close to unity. The inward rectifier K+ current (IK1) was not affected by rosiglitazone up to concentrations of 100 mM. Suppression of Ito, IKr, and ICa was confirmed also under action potential voltage clamp conditions.CONCLUSIONS AND IMPLICATIONSAlterations in the densities and kinetic properties of ion currents may carry serious pro-arrhythmic risk in case of overdose with rosiglitazone, especially in patients having multiple cardiovascular risk factors, like elderly diabetic patients.
Tárgyszavak:	Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban antidiabetic agents rosiglitazone dog cardiomyocytes action potential ion currents
Megjelenés:	British Journal Of Pharmacology 163 : 3 (2011), p. 499-509. -
További szerzők:	Harmati Gábor (1983-) (élettanász) Bárándi László (1984-) (élettanász) Simkó József (1974-) (belgyógyász, kardiológus) Horváth Balázs (1981-) (élettanász) Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Lőrincz István (1950-) (belgyógyász, kardiológus) Szebeni Andrea Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP A feszültségfüggő K-csatornák szerepe excitábilis sejtekben
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