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Pflugers Arch. 2012 Apr;463(4):537-48. doi: 10.1007/s00424-011-1061-z. Epub 2011 Dec 8.

Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade.

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Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 126 University Place, Glasgow, UK.

Erratum in

  • Pflugers Arch. 2014 May;466(5):1021.


Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K(+) currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K(+) currents (I(TO), I(KSUS) and I(K1)) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in I(TO) density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. I(K1) was reduced by 34% at -120 mV (p < 0.05). Neither I(KSUS), nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of I(TO)- and I(K1)-decrease could result in a 28% increase in APD(90). Chronic β-blockade did not alter mRNA or protein expression of the I(TO) pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in I(K1). A reduction in atrial I(TO) and I(K1) associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits.

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