The rs13376333 risk allele mimics the effect of atrial fibrillation on SK-current density and afterdepolarizations in human atrial myocytes
| Autor: | Jiménez-Sábado, Verónica, Tarifa, Carmen, Casabella, Sergi, Montiel, José, Rodriguez-Font, E., Olesen, M. S., Hove-Madsen, Leif |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | European Heart Journal. 43 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Trabajo presentado en el European Society of Cardiology Congress, celebrado en Barcelona (España), del 26 al 29 de agosto de 2022 Background: Various genome wide association studies have associated the single nucleotide polymorphism (SNP) rs13376333 with increased risk of atrial fibrillation. This SNP is intronic to the KCNN3 gene that codes for the small conductance calcium-activated potassium channel type 3 (SK3), but functional electrophysiological effects of the risk variant are not known. Purpose: This study aimed to study the effects of atrial fibrillation and the rs13376333 risk SNP on the apamine sensitive SK-current and on afterdepolarizations in human atrial myocytes. Methods: Myocytes were isolated from human right atrial samples, and subjected to perforated patch-clamp technique to measure the apamine (100 nM) sensitive SK-current elicited by a voltage-ramp protocol, spontaneous transient inward Na-Ca exchange currents (ITI) or afterdepolarizations at rest. To assess the impact of the rs13376333 risk variant, patients without atrial fibrillation were genotyped and divided into risk and control groups according to the genotype at rs13376333. Results: At membrane potentials above ¿40 mV, the SK-current density increased with increasing membrane potentials. At +20mV the density was significantly smaller (0.18±0.04 pA/pF) in 5 patients with atrial fibrillation than in 24 patients without this arrhythmia (0.65±0.12 pA/pF, p |
| Databáze: | OpenAIRE |
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