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

Result code in 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>

Alternative codes found

RIV/00216224:14110/22:00125324

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

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

Name of the periodical

Pflügers Archiv European Journal of Physiology

ISSN

0031-6768

e-ISSN

1432-2013

Volume of the periodical

474

Issue of the periodical within the volume

3

Country of publishing house

DE - GERMANY

Number of pages

11

Pages from-to

303-313

UT code for WoS article

000749021100001

EID of the result in the Scopus database

2-s2.0-85123955963