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001-es BibID:	BIBFORM072702
035-os BibID:	(WoS)000418522900035 (Scopus)85032657327 (PubMed)29066415
Első szerző:	Oravecz Kinga
Cím:	Inotropic effect of NCX inhibition depends on the relative activity of the reverse NCX assessed by a novel inhibitor ORM-10962 on canine ventricular myocytes / Kinga Oravecz, Anita Kormos, Andrea Gruber, Zoltán Márton, Zsófia Kohajda, Leila Mirzaei, Norbert Jost, Jouko Levijoki, Piero Pollesello, Tuula Koskelainen, Leena Otsomaa, András Tóth, Julius Gy. Papp, Péter P. Nánási, Gudrun Antoons, András Varró, Károly Acsai, Norbert Nagy
Dátum:	2018
ISSN:	0014-2999
Megjegyzések:	Na+/Ca2+ exchanger (NCX) is the main Ca2+ transporter in cardiac myocytes. Its inhibition could be expected to exert positive inotropic action by accumulation of cytosolic Ca2+ ([Ca2+]i). However, we have observed only a marginal positive inotropic effect upon selective inhibition of NCX, which was enhanced when forward activity was facilitated. Here we attempted to clarify the underlying mechanism of the limited inotropic action of selective NCX inhibition by a novel inhibitor ORM-10962 on canine ventricular myocytes. 1?M ORM-10962 reduced the Ca2+ content of sarcoplasmic reticulum (SR) when the reverse NCX was favoured, while SR Ca2+ content was increased by ORM-10962 under conditions favouring the forward activity, like elevation of [Ca2+]i. L-type Ca2+ current (ICa) was not affected by 1?M ORM-10962 in the absence of SR Ca2+ release, while ICa was suppressed by ORM-10962 during normal Ca2+ cycling. The apparent degree of forward NCX inhibition was dependent on the elevation of [Ca2+]i, suggesting that an increased driving force of forward NCX can also limit the accumulation of [Ca2+i]. We concluded that in healthy myocardium the possible positive inotropic potential of NCX inhibition is considerably weaker than it was expected earlier by theoretical assumptions. The underlying mechanism may involve the autoregulation of Ca2+ handling and/or the preserved inducibility of forward NCX by high [Ca2+]i. This limitation of selective NCX inhibition seen in undiseased myocardium requires further studies in failing heart, which may allow correct evaluation of the potential therapeutic value of selective NCX inhibitors in the treatment of heart failure.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	European Journal of Pharmacology. - 818 (2018), p. 278-286. -
További szerzők:	Kormos Anita Gruber Andrea Márton Zoltán Kohajda Zsófia Mirzaei, Leila Jost Norbert Levijoki, Jouko Pollesello, Piero Koskelainen, Tuula Otsomaa, Leena Tóth András Papp Gy. Julius (Szeged) Nánási Péter Pál (1956-) (élettanász) Antoons, Gudrun Varró András (1954-) (farmakológus, klinikai farmakológus) Acsai Károly Nagy Norbert
Pályázati támogatás:	NKFIH K-119992 NKFIH NKFIH K-115397 NKFIH NKFIH NN109904 NKFIH NKFIH ANN-113273 NKFIH NKFIH PD-125402 NKFIH GINOP-2.3.2-15-2016-00006 GINOP GINOP-2.3.2-15-2016-00012 GINOP GINOP-2.3.2-15-2016-040 GINOP NKFP_07_01-RYT07_AF Egyéb UNKP-16-3-IKT/147-1787/8/2016-ÖSZT-95 UNKP TÁMOP 4.2.4 TÁMOP EFOP-3.6.2-16-2017-00006.A/2-11-1-2012-0001 EFOP
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