Aminophylline at clinically relevant concentrations affects
inward rectifier potassium current in a dual way

J 2022

Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way

DOURADO RAMALHO, Nuno Jorge, Olga ŠVECOVÁ, Roman KULA, Milena ŠIMURDOVÁ, Jiří ŠIMURDA et. al.

Základní údaje

Originální název

Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way

Autoři

DOURADO RAMALHO, Nuno Jorge (620 Portugalsko, domácí), Olga ŠVECOVÁ (203 Česká republika, domácí), Roman KULA (203 Česká republika, domácí), Milena ŠIMURDOVÁ (203 Česká republika, domácí), Jiří ŠIMURDA (203 Česká republika, domácí) a Markéta BÉBAROVÁ (203 Česká republika, garant, domácí)

Vydání

Pflügers Archiv - European Journal of Physiology, Heidelberg, Springer, 2022, 0031-6768

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.500

Kód RIV

RIV/00216224:14110/22:00125324

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1007/s00424-021-02646-8

UT WoS

000749021100001

Klíčová slova anglicky

Aminophylline Inward rectifier; Dual effect; Arrhythmia; Fibrillation; Population channel model

Štítky

14110322, 14110515, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 19. 7. 2022 08:26, Mgr. Tereza Miškechová

Anotace

V originále

Bronchodilator aminophylline may induce atrial or less often ventricular arrhythmias. The mechanism of this proarrhythmic side effect has not been fully explained. Modifications of inward rectifier potassium (Kir) currents including IK1 are known to play an important role in arrhythmogenesis; however, no data on the aminophylline effect on these currents have been published. Hence, we tested the effect of aminophylline (3–100 µM) on IK1 in enzymatically isolated rat ventricular myocytes using the whole-cell patch-clamp technique. A dual steady-state effect of aminophylline was observed; either inhibition or activation was apparent in individual cells during the application of aminophylline at a given concentration. The smaller the magnitude of the control IK1, the more likely the activation of the current by aminophylline and vice versa. The effect was reversible; the relative changes at −50 and −110 mV did not differ. Using IK1 channel population model, the dual effect was explained by the interaction of aminophylline with two different channel populations, the first one being inhibited and the second one being activated. Considering various fractions of these two channel populations in individual cells, varying effects observed in the measured cells could be simulated. We propose that the dual aminophylline effect may be related to the direct and indirect effect of the drug on various Kir2.x subunits forming the homo- and heterotetrameric IK1 channels in a single cell. The observed IK1 changes induced by clinically relevant concentrations of aminophylline might contribute to arrhythmogenesis related to the use of this bronchodilator in clinical medicine.

Návaznosti

MUNI/A/1133/2021, interní kód MU

Název: Od buňky k medicíně (Akronym: CELLVIEW)

Investor: Masarykova univerzita, Od buňky k medicíně

MUNI/A/1246/2020, interní kód MU

Název: Kardiovaskulární systém: od iontového kanálu k celotělovému modelu (Akronym: KAVASYKAMO)

Investor: Masarykova univerzita, Kardiovaskulární systém: od iontového kanálu k celotělovému modelu

Citovat

DOURADO RAMALHO, Nuno Jorge, Olga ŠVECOVÁ, Roman KULA, Milena ŠIMURDOVÁ, Jiří ŠIMURDA a Markéta BÉBAROVÁ. Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way. Pflügers Archiv - European Journal of Physiology. Heidelberg: Springer, 2022, roč. 474, č. 3, s. 303-313. ISSN 0031-6768. Dostupné z: https://dx.doi.org/10.1007/s00424-021-02646-8.

@article{1830158,
   author = {Dourado Ramalho, Nuno Jorge and Švecová, Olga and Kula, Roman and Šimurdová, Milena and Šimurda, Jiří and Bébarová, Markéta},
   article_location = {Heidelberg},
   article_number = {3},
   doi = {http://dx.doi.org/10.1007/s00424-021-02646-8},
   keywords = {Aminophylline Inward rectifier; Dual effect; Arrhythmia; Fibrillation; Population channel model},
   language = {eng},
   issn = {0031-6768},
   journal = {Pflügers Archiv - European Journal of Physiology},
   title = {Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way},
   url = {https://link.springer.com/article/10.1007%2Fs00424-021-02646-8},
   volume = {474},
   year = {2022}
}

TY  - JOUR
ID  - 1830158
AU  - Dourado Ramalho, Nuno Jorge - Švecová, Olga - Kula, Roman - Šimurdová, Milena - Šimurda, Jiří - Bébarová, Markéta
PY  - 2022
TI  - Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way
JF  - Pflügers Archiv - European Journal of Physiology
VL  - 474
IS  - 3
SP  - 303-313
EP  - 303-313
PB  - Springer
SN  - 00316768
KW  - Aminophylline Inward rectifier
KW  - Dual effect
KW  - Arrhythmia
KW  - Fibrillation
KW  - Population channel model
UR  - https://link.springer.com/article/10.1007%2Fs00424-021-02646-8
N2  - Bronchodilator aminophylline may induce atrial or less often ventricular arrhythmias. The mechanism of this proarrhythmic side effect has not been fully explained. Modifications of inward rectifier potassium (Kir) currents including IK1 are known to play an important role in arrhythmogenesis; however, no data on the aminophylline effect on these currents have been published. Hence, we tested the effect of aminophylline (3–100 µM) on IK1 in enzymatically isolated rat ventricular myocytes using the whole-cell patch-clamp technique. A dual steady-state effect of aminophylline was observed; either inhibition or activation was apparent in individual cells during the application of aminophylline at a given concentration. The smaller the magnitude of the control IK1, the more likely the activation of the current by aminophylline and vice versa. The effect was reversible; the relative changes at −50 and −110 mV did not differ. Using IK1 channel population model, the dual effect was explained by the interaction of aminophylline with two different channel populations, the first one being inhibited and the second one being activated. Considering various fractions of these two channel populations in individual cells, varying effects observed in the measured cells could be simulated. We propose that the dual aminophylline effect may be related to the direct and indirect effect of the drug on various Kir2.x subunits forming the homo- and heterotetrameric IK1 channels in a single cell. The observed IK1 changes induced by clinically relevant concentrations of aminophylline might contribute to arrhythmogenesis related to the use of this bronchodilator in clinical medicine.
ER  -

DOURADO RAMALHO, Nuno Jorge, Olga ŠVECOVÁ, Roman KULA, Milena ŠIMURDOVÁ, Jiří ŠIMURDA a Markéta BÉBAROVÁ. Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way. \textit{Pflügers Archiv - European Journal of Physiology}. Heidelberg: Springer, 2022, roč.~474, č.~3, s.~303-313. ISSN~0031-6768. Dostupné z: https://dx.doi.org/10.1007/s00424-021-02646-8.

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