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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
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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001-es BibID:	BIBFORM009061
Első szerző:	Jost Norbert
Cím:	Contribution of I Kr and I K1 to ventricular repolarization in canine and human myocytes : is there any influence of action potential duration? / Jost, N., Acsai, K., Horvath, B., Banyasz, T., Baczko, I., Bitay, M., Bogats, G., Nanasi, P. P.
Dátum:	2009
ISSN:	0300-8428 (Print)
Megjegyzések:	The aim of the present work was to study the profile of the rapid delayed rectifier potassium current (I (Kr)) and the inward rectifier potassium current (I (K1)) during ventricular repolarization as a function of action potential duration and rate of repolarization. METHODS: Whole cell configuration of the patch clamp technique was used to monitor I (Kr) and I (K1) during the action potential plateau and terminal repolarization. Action potentials recorded at various cycle lengths (0.4-5 s) and repolarizing voltage ramps having various slopes (0.5-3 V/s) were used as command signals. I (Kr) and I (K1) were identified as difference currents dissected by E-4031 and BaCl(2), respectively. RESULTS: Neither peak amplitudes nor mean values of I (Kr) and I (K1) recorded during the plateau of canine action potentials were influenced by action potential duration. The membrane potential where I (Kr) and I (K1) peaked during the terminal repolarization was also independent of action potential duration. Similar results were obtained in undiseased human ventricular myocytes, and also in canine cells when I (Kr) and I (K1) were evoked using repolarizing voltage ramps of various slopes. Action potential voltage clamp experiments revealed that the peak values of I (Kr), I (K1), and net outward current during the terminal repolarization were independent of the pacing cycle length within the range of 0.4 and 5 s. CONCLUSIONS: The results indicate that action potential configuration fails to influence the amplitude of I (Kr) and I (K1) during the ventricular action potential in dogs and humans, suggesting that rate-dependent changes in action potential duration are not likely related to rate-dependent alterations in I (Kr) or I (K1) kinetics in these species.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Action Potentials Animals Barium Compounds Chlorides Dogs Electrophysiology Humans KATP Channels Kinetics Muscle Cells Patch-Clamp Techniques Potassium Channels, Inwardly Rectifying Reference Values Ventricular Function
Megjelenés:	Basic Research in Cardiology. - 104 : 1 (2009), p. 33-41. -
További szerzők:	Acsai Károly Horváth Balázs (1981-) (élettanász) Bányász Tamás (1960-) (élettanász) Baczkó István Bitay Miklós Bogáts Gábor Nánási Péter Pál (1956-) (élettanász)
Internet cím:	DOI elektronikus változat
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001-es BibID:	BIBFORM009105
Első szerző:	Nagy Norbert (kísérletes farmakológus)
Cím:	Does small-conductance calcium-activated potassium channel contribute to cardiac repolarization? / Nagy, N., Szuts, V., Horvath, Z., Seprenyi, G., Farkas, A. S., Acsai, K., Prorok, J., Bitay, M., Kun, A., Pataricza, J., Papp, J. G., Nanasi, P. P., Varro, A., Toth, A.
Dátum:	2009
ISSN:	0022-2828 (Print)
Megjegyzések:	Small-conductance calcium-activated potassium channels (SK channels) have a significant role in neurons. Since they directly integrate calcium handling with repolarization, in heart their role would be particularly important. However, their contribution to cardiac repolarization is still unclear. A previous study reported a significant lengthening effect of apamin, a selective SK channel inhibitor, on the action potential duration in atrial and ventricular mouse cardiomyocytes and human atrial cells. They concluded that these channels provide an important functional link between intracellular calcium handling and action potential kinetics. These findings seriously contradict our studies on cardiac "repolarization reserve", where we demonstrated that inhibition of a potassium current is not likely to cause excessive APD lengthening, since its decrease is mostly compensated by a secondary increase in other, unblocked potassium currents. To clarify this contradiction, we reinvestigated the role of the SK current in cardiac repolarization, using conventional microelectrode and voltage-clamp techniques in rat and dog atrial and ventricular multicellular preparations, and in isolated cardiomyocytes. SK2 channel expression was confirmed with immunoblot technique and confocal microscopy. We found, that while SK2 channels are expressed in the myocardium, a full blockade of these channels by 100 nM apamin--in contrast to the previous report--did not cause measurable electrophysiological changes in mammalian myocardium, even when the repolarization reserve was blunted. These results clearly demonstrate that in rat, dog and human ventricular cells under normal physiological conditions--though present--SK2 channels are not active and do not contribute to action potential repolarization.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal of Molecular and Cellular Cardiology. - 47 : 5 (2009), p. 656-663. -
További szerzők:	Szűts Viktória (farmakológus Szeged) Horváth Zoltán Seprényi György Farkas Attila (1961-) (farmakológus) Acsai Károly Prorok János Bitay Miklós Kun Attila Pataricza János Papp Gy. Julius (Szeged) Nánási Péter Pál (1956-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Tóth András (farmakológus)
Internet cím:	DOI elektronikus változat
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