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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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2.

001-es BibID:BIBFORM106377
035-os BibID:(cikkazonosító)446 (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
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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