Összesen 3 találat.


001-es BibID:BIBFORM016600
Első szerző:Bárándi László (élettanász)
Cím:Reverse rate-dependent changes are determined by baseline action potential duration in mammalian and human ventricular preparations / Bárándi László, Virág László, Jost Norbert, Horváth Zoltán, Koncz István, Papp Rita, Harmati Gábor, Horváth Balázs, Szentandrássy Norbert, Bányász Tamás, Magyar János, Zaza Antonio, Varró András, Nánási Péter P.
Megjegyzések:Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate-dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mechanisms responsible for RRD in mammalian ventricular myocardium. Action potentials were recorded using conventional sharp microelectrodes from human, canine, rabbit and guinea pig ventricular myocardium in a rate-dependent manner varying the cycle length (CL) between 0.3 and 5 s. Rate-dependent drug effects were studied using agents known to lengthen or shorten action potentials, and these drug-induced changes in APD were correlated with baseline APD values. Both drug-induced lengthening (by dofetilide, sotalol, E-4031, BaCl2, veratrine, BAY K 8644) and shortening (by mexiletine, tetrodotoxin, lemakalim) of action potentials displayed RRD, i.e., changes in APD were greater at longer than at shorter CLs. In rabbit, where APD is a biphasic function of CL, the drug-induced APD changes were proportional to baseline APD values but not to CL. Similar results were obtained when repolarization was modified by injection of inward or outward current pulses in isolated canine cardiomyocytes. In each case the change in APD was proportional to baseline APD (i.e., that measured before the superfusion of drug or injection of current). Also, the net membrane current (Inet), determined from the action potential waveform at the middle of the plateau, was inversely proportional to APD and consequently with to CL. The results indicate that RRD is a common characteristic of all the drugs tested regardless of the modified ion current species. Thus, drug-induced RRD can be considered as an intrinsic property of cardiac membranes based on the inverse relationship between Inet and APD.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Ventricular repolarization
Action potential duration
Reverse rate dependence
Membrane current
Human myocardium
Mammalian cardiac cells
egyetemen (Magyarországon) készült közlemény
Megjelenés:Basic Research In Cardiology. - 105 : 3 (2010), p. 315-323. -
További szerzők:Virág László (élettanász Szeged) Jost Norbert Horváth Zoltán Koncz István (Szeged) Papp Rita Harmati Gábor (1983-) (élettanász) Horváth Balázs (1981-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Zaza, Antonio Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
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Intézményi repozitóriumban (DEA) tárolt változat


001-es BibID:BIBFORM051689
035-os BibID:WOS:000326178500011
Első szerző:Jost Norbert
Cím:Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs / Norbert Jost, László Virág, Philippe Comtois, Balázs Ördög, Viktória Szuts, György Seprényi, Miklós Bitay, Zsófia Kohajda, István Koncz, Norbert Nagy, Tamás Szél, János Magyar, Mária Kovács, László G. Puskás, Csaba Lengyel, Erich Wettwer, Ursula Ravens, Péter P. Nánási, Julius Gy. Papp, András Varró, Stanley Nattel
Megjegyzések:Abstract The species-specific determinants of repolarization are poorly understood. Thisstudy compared the contribution of various currents to cardiac repolarization in canine andhuman ventricle.Conventional microelectrode,whole-cell patch-clamp,molecular biological andmathematical modelling techniques were used. Selective IKr block (50?100 nmol l?1 dofetilide)lengthened AP duration at 90% of repolarization (APD90) >3-fold more in human than dog,suggesting smaller repolarization reserve in humans. Selective IK1 block (10 ?mol l?1 BaCl2) andIKs block (1 ?mol l?1 HMR-1556) increased APD90 more in canine than human right ventricularpapillary muscle. Ion current measurements in isolated cardiomyocytes showed that IK1 and IKsdensities were 3- and 4.5-fold larger in dogs than humans, respectively. IKr density and kineticswere similar in human versus dog. ICa and Ito were respectively ?30% larger and ?29% smallerin human, and Na+?Ca2+ exchange current was comparable. Cardiac mRNA levels for the main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were significantly lower, butmRNA expression of ERG and KvLQT1 (IKr and IKs ?-subunits) were not significantly different,in human versus dog. Immunostaining suggested lower Kir2.1 and minK, and higher KvLQT1protein expression in human versus canine cardiomyocytes. IK1 and IKs inhibition increased theAPD-prolonging effect of IKr block more in dog (by 56% and 49%, respectively) than human(34 and 16%), indicating that both currents contribute to increased repolarization reserve inthe dog. A mathematical model incorporating observed human?canine ion current differencesconfirmed the role of IK1 and IKs in repolarization reserve differences. Thus, humans show greaterrepolarization-delaying effects of IKr block than dogs, because of lower repolarization reservecontributions from IK1 and IKs, emphasizing species-specific determinants of repolarization andthe limitations of animal models for human disease.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
L-type calcium current
action potential
dog heart
human heart
Megjelenés:Journal of Physiology-London. - 591 : 17 (2013), p. 4189-4206. -
További szerzők:Virág László (élettanász Szeged) Comtois, Philippe Ördög Balázs Szuts Viktória Seprényi György Bitay Miklós Kohajda Zsófia Koncz István (Szeged) Nagy Norbert (1977-) (kísérletes farmakológus) Szél Tamás Magyar János (1961-) (élettanász) Kovács Mária (Szeged) Puskás László G. Lengyel Csaba (Szeged) Wettwer, Erich Ravens, Ursula Nánási Péter Pál (1956-) (élettanász) Papp Gy. Julius (Szeged) Varró András (1954-) (farmakológus, klinikai farmakológus) Nattel, Stanley
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat


001-es BibID:BIBFORM016885
Első szerző:Virág László (élettanász Szeged)
Cím:Analysis of the contribution of Ito to repolarization in canine ventricular myocardium / Virág L., Jost N., Papp R., Koncz I., Kristóf A., Kohajda Z., Harmati G., Carbonell-Pascual B., Ferrero J. M. Jr., Papp J. Gy., Nánási P. P., Varró A.
Megjegyzések:Contribution of the transient outward potassium current (Ito) to ventricular repolarization is controversial depending on the experimental conditions, the region of myocardium or the species studied. The aim of the present study was, therefore, to characterize Ito and estimate its contribution to repolarization reserve in canine ventricular myocardium. Experimental approach: Ion currents were recorded using conventional whole cell voltage clamp and action potential voltage clamp techniques in isolated canine ventricular cells. Action potentials were recorded from canine ventricular preparations using microelectrodes. Key results: Contribution of Ito to repolarization was studied using 100 ?M chromanol 293B in full IKs blockade by 0.5 ?M HMR 1556. This high concentration of chromanol 293B effectively suppressed Ito without affecting other repolarizing K(+) currents (IK1, IKr, Ip). Action potential clamp experiments revealed a slowly inactivating and a "late" chromanol-sensitive current component flowing during the action potential plateau. Action potentials were significantly lengthened by chromanol 293B in the presence of HMR 1556. This lengthening effect of Ito inhibition showed reverse rate-dependent properties. It was extremely augmented after additional attenuation of repolarization reserve by 0.1 ?M dofetilide resulting in the occurrence of early afterdepolarizations (EADs). The results have been confirmed by computer simulation. Conclusions and Implications: The results indicate that Ito is involved in governing repolarization in canine ventricular myocardium and, it contributes significantly to the repolarization reserve. Therefore, blockade of Ito may enhance proarrhythmic risk.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
transient outward current
action potential duration
repolarization reserve
cardiac ventricular muscle
Megjelenés:British Journal Of Pharmacology. - 164 : 1 (2011), p. 93-105. -
További szerzők:Jost Norbert Papp R. Koncz István (Szeged) Kristóf A. (Szeged) Kohajda Zsófia Harmati Gábor (1983-) (élettanász) Carbonell-Pascual, B. Ferrero, J. M. Jr Papp Gy. Julius (Szeged) Nánási Péter Pál (1956-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus)
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
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