Marshall, G.E., Russell, J.A., Tellez, J.O., Jhund, P.S. , Currie, S., Dempster, J., Boyett, M.R., Kane, K.A., Rankin, A.C. and Workman, A.J. (2012) Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade. Pflügers Archiv - European Journal of Physiology, 463(4), pp. 537-548. (doi: 10.1007/s00424-011-1061-z)
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Publisher's URL: http://dx.doi.org/10.1007/s00424-011-1061-z
Abstract
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 (ITO, IKSUS and IK1) 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 ITO 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. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO 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 IK1. A reduction in atrial ITO and IK1 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Rankin, Professor Andrew and Marshall, Dr Gillian and Jhund, Professor Pardeep and Russell, Mrs Julie and Workman, Dr Antony |
| Authors: | Marshall, G.E., Russell, J.A., Tellez, J.O., Jhund, P.S., Currie, S., Dempster, J., Boyett, M.R., Kane, K.A., Rankin, A.C., and Workman, A.J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Pflügers Archiv - European Journal of Physiology |
| ISSN: | 0031-6768 |
| Published Online: | 01 January 2011 |
| First Published: | First published in Pflügers Archiv - European Journal of Physiology |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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