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.

Basic information

Original name

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

Authors

DOURADO RAMALHO, Nuno Jorge (620 Portugal, belonging to the institution), Olga ŠVECOVÁ (203 Czech Republic, belonging to the institution), Roman KULA (203 Czech Republic, belonging to the institution), Milena ŠIMURDOVÁ (203 Czech Republic, belonging to the institution), Jiří ŠIMURDA (203 Czech Republic, belonging to the institution) and Markéta BÉBAROVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.500

RIV identification code

RIV/00216224:14110/22:00125324

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000749021100001

Keywords in English

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

Abstract

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.

Links

MUNI/A/1133/2021, interní kód MU

Name: Od buňky k medicíně (Acronym: CELLVIEW)

Investor: Masaryk University

MUNI/A/1246/2020, interní kód MU

Name: Kardiovaskulární systém: od iontového kanálu k celotělovému modelu (Acronym: KAVASYKAMO)

Investor: Masaryk University

Citovat

DOURADO RAMALHO, Nuno Jorge, Olga ŠVECOVÁ, Roman KULA, Milena ŠIMURDOVÁ, Jiří ŠIMURDA and 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, vol. 474, No 3, p. 303-313. ISSN 0031-6768. Available from: 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 and 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, vol.~474, No~3, p.~303-313. ISSN~0031-6768. Available from: https://dx.doi.org/10.1007/s00424-021-02646-8.

Detailed Information on Publication Record