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001-es BibID:	BIBFORM024502
035-os BibID:	(WoS)000294414700002 (Scopus)80052005781
Első szerző:	Bányász Tamás (élettanász)
Cím:	Mechanism of reverse rate-dependent action of cardioactive agents / Tamás Bányász, László Bárándi, Gábor Harmati, László Virág, Norbert Szentandrássy, Ildikó Márton, Antonio Zaza, András Varró, Péter P. Nánási
Dátum:	2011
ISSN:	0929-8673 1875-533X
Megjegyzések:	Class 3 antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD), i.e. changes in APD are greater at longer than at shorter cycle lengths. In spite of the several theories developed to explain this reverse rate-dependency, its mechanism has been clarified only recently. The aim of the present study is to elucidate the mechanisms responsible for reverse rate-dependency in mammalian ventricular myocardium. Action potentials were recorded using conventional sharp microelectrodes from human, canine, rabbit, guinea pig, and rat ventricular myocardium in a rate-dependent manner. Rate-dependent drug-effects of various origin were studied using agents known to lengthen or shorten action potentials allowing thus to determine the drug-induced changes in APD as a function of the cycle length. Both drug-induced lengthening and shortening of action potentials displayed reverse rate-dependency in human, canine, and guinea pig preparations, but not in rabbit and rat myocardium. Similar results were obtained when repolarization was modified by injection of inward or outward current pulses in isolated canine cardiomyocytes. In contrast to reverse rate-dependence, drug-induced changes in APD well correlated with baseline APD values (i.e. that measured before the superfusion of drug or injection of current) in all of the preparations studied. Since the net membrane current (I(net)), determined from the action potential waveform at the middle of the plateau, was inversely proportional to APD, and consequently to cycle length, it is concluded that that reverse rate-dependency may simply reflect the inverse relationship linking I(net) to APD. In summary, reverse rate-dependency is an intrinsic property of drug action in the hearts of species showing positive APD - cycle length relationship, including humans. This implies that development of a pure K(+) channel blocking agent without reverse rate-dependent effects is not likely to be successful.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk antiarrhythmiás szerek APD Molekuláris Medicina egyetemen (Magyarországon) készült közlemény
Megjelenés:	Current medicinal chemistry. - 18 : 24 (2011), p. 3597-3606. -
További szerzők:	Bárándi László (1984-) (élettanász) Harmati Gábor (1983-) (élettanász) Virág László (élettanász Szeged) Szentandrássy Norbert (1976-) (élettanász) Márton Ildikó (1954-) (fogszakorvos) Zaza, Antonio Varró András (1954-) (farmakológus, klinikai farmakológus) 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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