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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F22%3A00076109" target="_blank" >RIV/65269705:_____/22:00076109 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/22:00125324

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s00424-021-02646-8" target="_blank" >https://link.springer.com/article/10.1007/s00424-021-02646-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00424-021-02646-8" target="_blank" >10.1007/s00424-021-02646-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 I-K1 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 mu M) on I-K1 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 I-K1, 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 I-K1 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 I-K1 channels in a single cell. The observed I-K1 changes induced by clinically relevant concentrations of aminophylline might contribute to arrhythmogenesis related to the use of this bronchodilator in clinical medicine.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 I-K1 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 mu M) on I-K1 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 I-K1, 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 I-K1 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 I-K1 channels in a single cell. The observed I-K1 changes induced by clinically relevant concentrations of aminophylline might contribute to arrhythmogenesis related to the use of this bronchodilator in clinical medicine.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pflügers Archiv European Journal of Physiology

ISSN

0031-6768

e-ISSN

1432-2013

Svazek periodika

474

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

303-313

Kód UT WoS článku

000749021100001

EID výsledku v databázi Scopus

2-s2.0-85123955963