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001-es BibID:	BIBFORM051689
035-os BibID:	(Scopus)84883281759 (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
Dátum:	2013
ISSN:	0022-3751
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 repolarization
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
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