Inhibitory Effects of Dronedarone on Small Conductance Calcium Activated Potassium Channels in Patients with Chronic Atrial Fibrillation: Comparison to Amiodarone.
Med Sci Monit
; 26: e924215, 2020 May 29.
Article
em En
| MEDLINE
| ID: mdl-32470968
ABSTRACT
BACKGROUND Dysfunction of small conductance calcium activated potassium (SK) channels plays a vital role in atrial arrhythmogenesis. Amiodarone and dronedarone are the most effective class III antiarrhythmic drugs. It is unclear whether the antiarrhythmic effect of amiodarone and dronedarone is related to SK channel inhibition. MATERIAL AND METHODS Tissue samples were obtained from the right atria of 46 patients with normal sinus rhythm and 39 patients with chronic atrial fibrillation. Isolated atrial myocytes were obtained by enzymatic dissociation. KCNN2 (SK2) channels were transiently expressed in human embryonic kidney (HEK)-293 cells. SK currents were recorded using whole-cell conventional patch clamp techniques. RESULTS Amiodarone and dronedarone showed a concentration-dependent inhibitory effect on SK currents (IKAS) in atrial myocytes from normal sinus rhythm patients and chronic atrial fibrillation patients. The suppressed efficacy of dronedarone and amiodarone on IKAS was greater in atrial myocytes from chronic atrial fibrillation patients than that from normal sinus rhythm patients. Furthermore, in patients with chronic atrial fibrillation, the IC50 value was 2.42 µM with dronedarone and 8.03 µM with amiodarone. In HEK-293 cells with transiently transfected SK2 channels, both dronedarone and amiodarone had a dose-dependent inhibitory effect on IKAS. The IC50 value was 1.7 µM with dronedarone and 7.2 µM with amiodarone in cells from patients with chronic atrial fibrillation. Compared to amiodarone, dronedarone is more efficacy to inhibit IKAS and could be a potential intervention for patients with chronic atrial fibrillation. CONCLUSIONS Dronedarone provides a great degree of IKAS inhibition in atrial myocytes from chronic atrial fibrillation than amiodarone. IKAS might be a potential target of amiodarone and dronedarone for the management of chronic atrial fibrillation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
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Canais de Potássio Ativados por Cálcio de Condutância Baixa
/
Dronedarona
Limite:
Adult
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Med Sci Monit
Assunto da revista:
MEDICINA
Ano de publicação:
2020
Tipo de documento:
Article