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001-es BibID:	BIBFORM096191
035-os BibID:	(cikkazonosító)9499 (scopus)85114049778 (wos)000694373200001
Első szerző:	Dienes Csaba (gyógyszerész)
Cím:	Electrophysiological Effects of the Transient Receptor Potential Melastatin 4 Channel Inhibitor (4-Chloro-2-(2-chlorophenoxy)acetamido) Benzoic Acid (CBA) in Canine Left Ventricular Cardiomyocytes / Csaba Dienes, Tamás Hézső, Dénes Zsolt Kiss, Dóra Baranyai, Zsigmond Máté Kovács, László Szabó, János Magyar, Tamás Bányász, Péter P. Nánási, Balázs Horváth, Mónika Gönczi, Norbert Szentandrássy
Dátum:	2021
ISSN:	1661-6596 1422-0067
Megjegyzések:	Transient receptor potential melastatin 4 (TRPM4) plays an important role in many tissues, including pacemaker and conductive tissues of the heart, but much less is known about its electrophysiological role in ventricular myocytes. Our earlier results showed the lack of selectivity of 9-phenanthrol, so CBA ((4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) was chosen as a new, potentially selective inhibitor. Goal: Our aim was to elucidate the effect and selectivity of CBA in canine left ventricular cardiomyocytes and to study the expression of TRPM4 in the canine heart. Experiments were carried out in enzymatically isolated canine left ventricular cardiomyocytes. Ionic currents were recorded with an action potential (AP) voltage-clamp technique in whole-cell configuration at 37 ?C. An amount of 10 mM BAPTA was used in the pipette solution to exclude the potential activation of TRPM4 channels. AP was recorded with conventional sharp microelectrodes. CBA was used in 10 ?M concentrations. Expression of TRPM4 protein in the heart was studied by Western blot. TRPM4 protein was expressed in the wall of all four chambers of the canine heart as well as in samples prepared from isolated left ventricular cells. CBA induced an approximately 9% reduction in AP duration measured at 75 and 90% of repolarization and decreased the short-term variability of APD90. Moreover, AP amplitude was increased and the maximal rates of phase 0 and 1 were reduced by the drug. In AP clamp measurements, CBA-sensitive current contained a short, early outward and mainly a long, inward current. Transient outward potassium current (Ito) and late sodium current (INa,L) were reduced by approximately 20 and 47%, respectively, in the presence of CBA, while L-type calcium and inward rectifier potassium currents were not affected. These effects of CBA were largely reversible upon washout. Based on our results, the CBA induced reduction of phase-1 slope and the slight increase of AP amplitude could have been due to the inhibition of Ito. The tendency for AP shortening can be explained by the inhibition of inward currents seen in AP-clamp recordings during the plateau phase. This inward current reduced by CBA is possibly INa,L, therefore, CBA is not entirely selective for TRPM4 channels. As a consequence, similarly to 9-phenanthrol, it cannot be used to test the contribution of TRPM4 channels to cardiac electrophysiology in ventricular cells, or at least caution must be applied.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk CBA TRPM4 cardiac ionic currents cardiac action potentials canine myocytes action potential voltage clamp
Megjelenés:	International Journal Of Molecular Sciences. - 22 : 17 (2021), p. 9499. -
További szerzők:	Hézső Tamás (1993-) (élettanász) Kiss Dénes Zsolt (1995-) (orvos, élettanász) Baranyai Dóra Kovács Zsigmond Máté (1995-) (orvos) Szabó László (1994-) (molekuláris biológus) Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Horváth Balázs (1981-) (élettanász) Gönczi Mónika (1974-) (élettanász) Szentandrássy Norbert (1976-) (élettanász)
Pályázati támogatás:	NKFIH-K115397 Egyéb NKFIH-K138090 Egyéb NKFIH-FK128116 Egyéb GINOP-2.3.2-15-2016-00040 GINOP EFOP-3.6.2-16-2017-00006 EFOP DE-SPACE(TKP-2020-NKA-04) Egyéb EFOP-3.6.3-VEKOP-16-2017-00009 EFOP ÚNKP-20-3 Egyéb ÚNKP-20-2 Egyéb
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001-es BibID:	BIBFORM125611
035-os BibID:	(Scopus)85208586610 (WoS)001352275300001
Első szerző:	Kovács Zsigmond Máté (orvos)
Cím:	Beta-Adrenergic Activation of the Inward Rectifier K+ Current Is Mediated by the CaMKII Pathway in Canine Ventricular Cardiomyocytes / Zsigmond Máté Kovács, Balázs Horváth, Csaba Dienes, József Óvári, Dénes Kiss, Tamás Hézső, Norbert Szentandrássy, János Magyar, Tamás Bányász, Péter Pál Nánási
Dátum:	2024
ISSN:	1661-6596 1422-0067
Megjegyzések:	Several ion currents in the mammalian ventricular myocardium are substantially regulated by the sympathetic nervous system via ?-adrenergic receptor activation, including the slow delayed rectifier K+ current and the L-type calcium current. This study investigated the downstream mechanisms of ?-adrenergic receptor stimulation by isoproterenol (ISO) on the inward rectifier (IK1) and the rapid delayed rectifier (IKr) K+ currents using action potential voltage clamp (APVC) and conventional voltage clamp techniques in isolated canine left ventricular cardiomyocytes. IK1 and IKr were dissected by 50 ?M BaCl2 and 1 ?M E-4031, respectively. Acute application of 10 nM ISO significantly increased IK1 under the plateau phase of the action potential (0?+20 mV) using APVC, and similar results were obtained with conventional voltage clamp. However, ?-adrenergic receptor stimulation did not affect the peak current density flowing during terminal repolarization or the overall IK1 integral. The ISO-induced enhancement of IK1 was blocked by the calcium/calmodulin kinase II (CaMKII) inhibitor KN-93 (1 ?M) but not by the protein kinase A inhibitor H-89 (3 ?M). Neither KN-93 nor H-89 affected the IK1 density under baseline conditions (in the absence of ISO). In contrast, parameters of the IKr current were not affected by ?-adrenergic receptor stimulation with ISO. These findings suggest that sympathetic activation enhances IK1 in canine left ventricular cells through the CaMKII pathway, while IKr remains unaffected under the experimental conditions used.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk inward rectifier K+ current rapid delayed rectifier K+ current sympathetic activation protein kinase A calcium/calmodulin-dependent protein kinase II action potential voltage clamp canine cardiomyocytes
Megjelenés:	International Journal Of Molecular Sciences. - 25 : 21 (2024), p. 1-14. -
További szerzők:	Horváth Balázs (1981-) (élettanász) Dienes Csaba (1995-) (gyógyszerész) Óvári József (1997-) (PhD hallgató) Kiss Dénes Zsolt (1995-) (orvos, élettanász) Hézső Tamás (1993-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:	NKFIH-K138090 Egyéb NKFIH-K142764 Egyéb NKFIH-K14730 Egyéb EKÖP-24-4-I-DE-455 Egyéb EKÖP-24-3-II-DE-154 Egyéb
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001-es BibID:	BIBFORM106377
035-os BibID:	(WOS)000910182000001 (Scopus)85145970899
Első szerző:	Ráduly Arnold Péter
Cím:	The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo : Implications for Clinical Applications / Ráduly Arnold Péter, Sárkány Fruzsina, Kovács Máté Balázs, Bernát Brigitta, Juhász Béla, Szilvássy Zoltán, Porszász Róbert, Horváth Balázs, Szentandrássy Norbert, Nánási Péter, Csanádi Zoltán, Édes István, Tóth Attila, Papp Zoltán, Priksz Dániel, Borbély Attila
Dátum:	2023
ISSN:	1422-0067
Megjegyzések:	Recent cardiotropic drug developments have focused on cardiac myofilaments. Danicamtiv, the second direct myosin activator, has achieved encouraging results in preclinical and clinical studies, thus implicating its potential applicability in the treatment of heart failure with reduced ejection fraction (HFrEF). Here, we analyzed the inotropic effects of danicamtiv in detail. To this end, changes in sarcomere length and intracellular Ca2+ levels were monitored in parallel, in enzymatically isolated canine cardiomyocytes, and detailed echocardiographic examinations were performed in anesthetized rats in the absence or presence of danicamtiv. The systolic and diastolic sarcomere lengths decreased; contraction and relaxation kinetics slowed down with increasing danicamtiv concentrations without changes in intracellular Ca2+ transients in vitro. Danicamtiv evoked remarkable increases in left ventricular ejection fraction and fractional shortening, also reflected by changes in systolic strain. Nevertheless, the systolic ejection time was significantly prolonged, the ratio of diastolic to systolic duration was reduced, and signs of diastolic dysfunction were also observed upon danicamtiv treatment in vivo. Taken together, danicamtiv improves cardiac systolic function, but it can also limit diastolic performance, especially at high drug concentrations.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk heart failure with reduced ejection fraction myosin activators danicamtiv positive inotropy strain diastolic dysfunction
Megjelenés:	International Journal Of Molecular Sciences. - 24 : 1 (2023), p. 446. -
További szerzők:	Sárkány Fruzsina (1996-) (orvos) Kovács Máté Balázs Bernát Brigitta (1997-) (farmakológus) Juhász Béla (1978-) (kísérletes farmakológus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Pórszász Róbert (1965-) (farmakológus, klinikai farmakológus) Horváth Balázs (1981-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Csanádi Zoltán (1960-) (kardiológus) Édes István (1952-) (kardiológus) Tóth Attila (1971-) (biológus) Papp Zoltán (1965-) (kardiológus, élettanász) Priksz Dániel (1989-) (farmakológus) Borbély Attila (1978-) (kardiológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00043 GINOP ÚNKP-21-3 Egyéb TKP2020-IKA-04 Egyéb TKP2020-NKA-04 Egyéb 2020-4.1.1-TKP2020 Egyéb NFKIH - K 132623 Egyéb NKFIH-K138090 Egyéb NKFIH-K142764 Egyéb NKFIH-FK128116 Egyéb
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