The contribution of ionic currents to changes in refractoriness of human atrial myocytes associated with chronic atrial fibrillation

Workman, A.J., Kane, K.A. and Rankin, A.C. (2001) The contribution of ionic currents to changes in refractoriness of human atrial myocytes associated with chronic atrial fibrillation. Cardiovascular Research, 52(2), pp. 226-235. (doi: 10.1016/S0008-6363(01)00380-7)

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Publisher's URL: http://dx.doi.org/10.1016/S0008-6363(01)00380-7

Abstract

<b>Objective:</b> To investigate changes in human atrial single cell functional electrophysiological properties associated with chronic atrial fibrillation (AF), and the contribution to these of accompanying ion current changes. <b>Methods:</b> The whole cell patch clamp technique was used to record action potentials, the effective refractory period (ERP) and ion currents, in the absence and presence of drugs, in enzymatically isolated myocytes from 11 patients with chronic (<6 months) AF and 39 patients in sinus rhythm. <b>Results:</b> Stimulation at high rates (up to 600 beats/min) markedly shortened late repolarisation and the ERP in cells from patients in sinus rhythm, and depolarised the maximum diastolic potential (MDP). Chronic AF was associated with a reduction in the ERP at physiological rate (from 203±16 to 104±15 ms, P<0.05), and marked attenuation in rate effects on the ERP and repolarisation. The abbreviated terminal phase of repolarisation prevented fast rate-induced depolarisation of the MDP in cells from patients with AF. The density of L-type Ca<sup>2+</sup> (<i>I</i><sub>CaL</sub>) and transient outward K<sup>+</sup> (<i>I</i><sub>TO</sub>) currents was significantly reduced in cells from patients with AF (by 60–65%), whilst the inward rectifier K<sup>+</sup> current (IK1) was increased, and the sustained outward current (<i>I</i><sub>KSUS</sub>) was unaltered. Superfusion of cells from patients in sinus rhythm with nifedipine (10 micromol/l) moderately shortened repolarisation, but had no effect on the ERP (228±12 vs. 225±11 ms). 4-Aminopyridine (2 mmol/l) markedly prolonged repolarisation and the ERP (by 35%, P<0.05). However, the combination of these drugs had no effect on late repolarisation or refractoriness. <b>Conclusion:</b> Chronic AF in humans is associated with attenuation in adaptation of the atrial single cell ERP and MDP to fast rates, which may not be explained fully by accompanying changes in <i>I</i><sub>CaL</sub> and <i>I</i><sub>TO</sub>.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rankin, Professor Andrew and Workman, Dr Antony
Authors: Workman, A.J., Kane, K.A., and Rankin, A.C.
Subjects:Q Science > QP Physiology
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
Journal Name:Cardiovascular Research
Publisher:Elsevier
ISSN:0008-6363
Copyright Holders:Copyright © 2001 Elsevier
First Published:First published in Cardiovascular Research 52(2):226-235
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.
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