Aminophylline at clinically relevant concentrations affects
inward rectifier potassium current in healthy porcine and
failing human cardiomyocytes in a similar manner

J 2024

Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in healthy porcine and failing human cardiomyocytes in a similar manner

BÉBAROVÁ, Markéta; Olga ŠVECOVÁ; Roman KULA; Michal PÁSEK; Edita JEKLOVÁ et al.

Základní údaje

Originální název

Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in healthy porcine and failing human cardiomyocytes in a similar manner

Autoři

BÉBAROVÁ, Markéta ; Olga ŠVECOVÁ ; Roman KULA ; Michal PÁSEK; Edita JEKLOVÁ; Petr FILA a Martin PEŠL

Vydání

Biomedicine & Pharmacotherapy, ISSY-LES-MOULINEAUX, ELSEVIER, 2024, 0753-3322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Francie

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.500

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/24:00137972

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Aminophylline; Arrhythmia; Inward rectifier; Action potential; Pig; Human

Štítky

14110115, 14110211, 14110515, 14110911

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 2. 2025 14:09, Mgr. Tereza Miškechová

Anotace

V originále

Aminophylline, a bronchodilator mainly used to treat severe asthma attacks, may induce arrhythmias. Unfortunately, the underlying mechanism is not well understood. We have recently described a significant, on average inhibitory effect of aminophylline on inward rectifier potassium current IK1, known to substantially contribute to arrhythmogenesis, in rat ventricular myocytes at room temperature. This study was aimed to examine whether a similar effect may be observed under clinically relevant conditions. Experiments were performed using the whole cell patch clamp technique at 37°C on enzymatically isolated healthy porcine and failing human ventricular myocytes. The effect of clinically relevant concentrations of aminophylline (10–100 µM) on IK1 did not significantly differ in healthy porcine and failing human ventricular myocytes. IK1 was reversibly inhibited by ∼20 and 30 % in the presence of 30 and 100 µM aminophylline, respectively, at −110 mV; an analogical effect was observed at −50 mV. To separate the impact of IK1 changes on AP configuration, potentially interfering ionic currents were blocked (L-type calcium and delayed rectifier potassium currents). A significant prolongation of AP duration was observed in the presence of 100 µM aminophylline in porcine cardiomyocytes which well agreed with the effect of a specific IK1 inhibitor Ba2+ (10 µM) and with the result of simulations using a porcine ventricular cell model. We conclude that the observed effect of aminophylline on healthy porcine and failing human IK1 might be involved in its proarrhythmic action. To fully understand the underlying mechanism, potential aminophylline impact on other ionic currents should be explored.

Návaznosti

MUNI/A/1547/2023, interní kód MU

Název: Analýza (dys)funkce: od molekul k živému organismu

Investor: Masarykova univerzita, Analýza (dys)funkce: od molekul k živému organismu

NU20-06-00156, projekt VaV

Název: Vliv pneumologické medikace na funkce lidských kardiomyocytů.

Investor: Ministerstvo zdravotnictví ČR, Vliv pneumologické medikace na funkce lidských kardiomyocytů, Podprogram 1 - standardní

NU22-02-00348, projekt VaV

Název: Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus

Investor: Ministerstvo zdravotnictví ČR, Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus, Podprogram 1 - standardní

Citovat

BÉBAROVÁ, Markéta; Olga ŠVECOVÁ; Roman KULA; Michal PÁSEK; Edita JEKLOVÁ; Petr FILA a Martin PEŠL. Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in healthy porcine and failing human cardiomyocytes in a similar manner. Biomedicine & Pharmacotherapy. ISSY-LES-MOULINEAUX: ELSEVIER, 2024, roč. 181, December 2024, s. 1-9. ISSN 0753-3322. Dostupné z: https://doi.org/10.1016/j.biopha.2024.117733.

@article{2459407,
   author = {Bébarová, Markéta and Švecová, Olga and Kula, Roman and Pásek, Michal and Jeklová, Edita and Fila, Petr and Pešl, Martin},
   article_location = {ISSY-LES-MOULINEAUX},
   article_number = {December 2024},
   doi = {https://doi.org/10.1016/j.biopha.2024.117733},
   keywords = {Aminophylline; Arrhythmia; Inward rectifier; Action potential; Pig; Human},
   language = {eng},
   issn = {0753-3322},
   journal = {Biomedicine & Pharmacotherapy},
   title = {Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in healthy porcine and failing human cardiomyocytes in a similar manner},
   url = {https://www.sciencedirect.com/science/article/pii/S0753332224016196?via%3Dihub},
   volume = {181},
   year = {2024}
}

TY  - JOUR
ID  - 2459407
AU  - Bébarová, Markéta - Švecová, Olga - Kula, Roman - Pásek, Michal - Jeklová, Edita - Fila, Petr - Pešl, Martin
PY  - 2024
TI  - Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in healthy porcine and failing human cardiomyocytes in a similar manner
JF  - Biomedicine & Pharmacotherapy
VL  - 181
IS  - December 2024
SP  - 1-9
EP  - 1-9
PB  - ELSEVIER
SN  - 07533322
KW  - Aminophylline
KW  - Arrhythmia
KW  - Inward rectifier
KW  - Action potential
KW  - Pig
KW  - Human
UR  - https://www.sciencedirect.com/science/article/pii/S0753332224016196?via%3Dihub
N2  - Aminophylline, a bronchodilator mainly used to treat severe asthma attacks, may induce arrhythmias. Unfortunately, the underlying mechanism is not well understood. We have recently described a significant, on average inhibitory effect of aminophylline on inward rectifier potassium current IK1, known to substantially contribute to arrhythmogenesis, in rat ventricular myocytes at room temperature. This study was aimed to examine whether a similar effect may be observed under clinically relevant conditions. Experiments were performed using the whole cell patch clamp technique at 37°C on enzymatically isolated healthy porcine and failing human ventricular myocytes. The effect of clinically relevant concentrations of aminophylline (10–100 µM) on IK1 did not significantly differ in healthy porcine and failing human ventricular myocytes. IK1 was reversibly inhibited by ∼20 and 30 % in the presence of 30 and 100 µM aminophylline, respectively, at −110 mV; an analogical effect was observed at −50 mV. To separate the impact of IK1 changes on AP configuration, potentially interfering ionic currents were blocked (L-type calcium and delayed rectifier potassium currents). A significant prolongation of AP duration was observed in the presence of 100 µM aminophylline in porcine cardiomyocytes which well agreed with the effect of a specific IK1 inhibitor Ba2+ (10 µM) and with the result of simulations using a porcine ventricular cell model. We conclude that the observed effect of aminophylline on healthy porcine and failing human IK1 might be involved in its proarrhythmic action. To fully understand the underlying mechanism, potential aminophylline impact on other ionic currents should be explored.
ER  -

BÉBAROVÁ, Markéta; Olga ŠVECOVÁ; Roman KULA; Michal PÁSEK; Edita JEKLOVÁ; Petr FILA a Martin PEŠL. Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in healthy porcine and failing human cardiomyocytes in a similar manner. \textit{Biomedicine \&{} Pharmacotherapy}. ISSY-LES-MOULINEAUX: ELSEVIER, 2024, roč.~181, December 2024, s.~1-9. ISSN~0753-3322. Dostupné z: https://doi.org/10.1016/j.biopha.2024.117733.

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