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001-es BibID:BIBFORM083023
035-os BibID:(WoS)000522138400002 (Scopus)85078193947 (PubMed)31958464
Első szerző:Horváth Balázs (élettanász)
Cím:Late sodium current in human, canine and guinea pig ventricular myocardium / Balázs Horváth, Tamás Hézső, Norbert Szentandrássy, Kornél Kistamás, Tamás Árpádffy-Lovas, Richárd Varga, Péter Gazdag, Roland Veress, Csaba Dienes, Dóra Baranyai, János Almássy, László Virág, Norbert Nagy, István Baczkó, János Magyar, Tamás Bányász, András Varró, Péter P. Nánási
Dátum:2020
ISSN:0022-2828
Megjegyzések:Although late sodium current (INa-late) has long been known to contribute to plateau formation of mammalian cardiac action potentials, lately it was considered as possible target for antiarrhythmic drugs. However, many aspects of this current are still poorly understood. The present work was designed to study the true profile of INa-late in canine and guinea pig ventricular cells and compare them to INa-late recorded in undiseased human hearts. INa-late was defined as a tetrodotoxin-sensitive current, recorded under action potential voltage clamp conditions using either canonic- or self-action potentials as command signals. Under action potential voltage clamp conditions the amplitude of canine and human INa-late monotonically decreased during the plateau (decrescendo-profile), in contrast to guinea pig, where its amplitude increased during the plateau (crescendo profile). The decrescendo-profile of canine INa-late could not be converted to a crescendo-morphology by application of ramp-like command voltages or command action potentials recorded from guinea pig cells. Conventional voltage clamp experiments revealed that the crescendo INa-late profile in guinea pig was due to the slower decay of INa-late in this species. When action potentials were recorded from multicellular ventricular preparations with sharp microelectrode, action potentials were shortened by tetrodotoxin, which effect was the largest in human, while smaller in canine, and the smallest in guinea pig preparations. It is concluded that important interspecies differences exist in the behavior of INa-late. At present canine myocytes seem to represent the best model of human ventricular cells regarding the properties of INa-late. These results should be taken into account when pharmacological studies with INa-late are interpreted and extrapolated to human. Accordingly, canine ventricular tissues or myocytes are suggested for pharmacological studies with INa-late inhibitors or modifiers. Incorporation of present data to human action potential models may yield a better understanding of the role of INa-late in action potential morphology, arrhythmogenesis, and intracellular calcium dynamics.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Late Na+ current
Ventricular repolarization
Action potential voltage clamp
Dog myocytes
Human myocytes
Megjelenés:Journal of Molecular and Cellular Cardiology. - 139 (2020), p. 14-23. -
További szerzők:Hézső Tamás (1993-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Kistamás Kornél (1986-) (biológus) Árpádffy-Lovas Tamás Varga Richárd Gazdag Péter Veress Roland (1992-) (molekuláris biológus) Dienes Csaba (1995-) (gyógyszerész) Baranyai Dóra Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító) Virág László (élettanász Szeged) Nagy Norbert (1977-) (kísérletes farmakológus) Baczkó István Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:GINOP-2.3.2.-15-2016-00040
GINOP
EFOP-3.6.2-16-2017-00006
EFOP
ÚNKP-19-4
Egyéb
ÚNKP-19-2
Egyéb
NKFIH-K115397
NKFIH
NKFIH-PD120794
NKFIH
NKFIH-FK128116
NKFIH
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