Role of constitutively active acetylcholine-mediated potassium current in atrial contractile dysfunction caused by atrial tachycardia remodelling.
Europace
; 12(10): 1490-7, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20682556
ABSTRACT
AIMS:
Atrial fibrillation (AF)-induced contractile dysfunction contributes importantly to thrombo-embolic stroke, the most serious AF complication. Atrial cardiomyocytes have a constitutively active acetylcholine-regulated K(+)-current (I(KAChc)) that is enhanced by atrial tachycardia (AT). I(KAChc) contributes to action potential duration (APD) shortening in AT-remodelled atrial cardiomyocytes; APD regulates contractility by controlling Ca(2+)-loading and systolic Ca(2+)-release. This study investigated the potential role of I(KAChc) in AF-related contractile dysfunction. METHODS ANDRESULTS:
Dogs were divided into two groups (i) unpaced control (CTL); (ii) AT (400 bpm for at least 7 days). Tertiapin-Q (TQ), a selective I(KAChc) blocker, was used to define I(KAChc) contributions to contractility. Single-cell left atrial (LA) intracellular Ca(2+)-transients (CaTrs), cell-shortening (CS), and whole LA tissue tension-generation were measured. Atrial tachycardia increased I(KAChc). Whole LA contractility was decreased in AT (0.17 ± 0.05 g) compared with CTL (0.40 ± 0.09 g), with significant reversal (0.30 ± 0.06 g) after TQ administration. Ca(2+)-transient amplitude and CS in single-cell were decreased by AT compared with CTL (167 ± 14 vs. 88 ± 10 nM; 10.3 ± 1.3 vs. 1.7 ± 0.3 µm, respectively; P < 0.001). The AT-induced reductions in single-cell CaTr amplitude and CS were partly reversed by TQ administration (88 ± 10 vs. 112 ± 16 nM; P < 0.001; 1.7 ± 0.3 vs. 3.6 ± 0.7 µm; P < 0.01). We then measured CaTr and CS with carbachol and/or TQ to vary I(KACh) at various extracellular [Ca(2+)]. The CaTr-CS relationship was linear and AT results fell on the regression line, indicating that AT-remodelling effects on contractility are attributable to reduced CaTr.CONCLUSION:
Up-regulated I(KAChc) contributes to AF-related contractile dysfunction and could be a novel target to prevent hypocontractility-related thrombo-embolic complications.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fibrilación Atrial
/
Taquicardia
/
Tromboembolia
/
Canales de Potasio
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Acetilcolina
/
Contracción Miocárdica
Límite:
Animals
Idioma:
En
Revista:
Europace
Asunto de la revista:
CARDIOLOGIA
/
FISIOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Corea del Sur