Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation

Workman, A.J., Kane, K.A. and Rankin, A.C. (2003) Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation. Cardiovascular Research, 59(3), pp. 593-602. (doi: 10.1016/S0008-6363(03)00466-8)

Abstract

<b>Objective:</b> To assess the contribution of the Na, K pump current (<i>I</i>_p) to the action potential duration (APD) and effective refractory period (ERP) in human atrial cells, and to investigate whether <i>I</i>_p contributes to the changes in APD and ERP associated with chronic atrial fibrillation (AF). <b>Methods:</b> Action potentials and ion currents were recorded by whole-cell patch clamp in atrial myocytes isolated from consenting patients undergoing cardiac surgery, who were in sinus rhythm (SR) or AF (>3 months). <b>Results:</b> In cells from patients in SR, the <i>I</i>_p blocker, ouabain (10 μM) significantly depolarised the membrane potential, Vm, from -80±2 (mean±S.E.) to -73±2 mV, and lengthened both the APD (174±17 vs. 197±23 ms at 90% repolarisation) and ERP (198±22 vs. 266±14 ms; P<0.05 for each, Student's t-test, <i>n</i>=7 cells, 5 patients). With an elevated pipette [Na⁺] of 30 mM, <i>I</i>_p was measured by increasing extracellular [K⁺] ([K⁺]o) from 0 to 5.4 mM. This produced an outward shift in holding current at -40 mV, abolished by 10 muM ouabain. K± and ouabain-sensitive current densities were similar, at 0.99±0.13 and 1.12±0.11 pA/pF, respectively (P>0.05; <i>n</i>=9 cells), confirming the K±induced current as <i>I</i>_p. <i>I</i>_p increased linearly with increasing Vm between -120 and +60 mV (<i>n</i>=25 cells). Stepwise increments in [K⁺]_o (between 0 and 10 mM) increased Ip in a concentration-dependent manner (maximum response, <i>E</i>_max=1.19±0.09 pA/pF; EC50=1.71±0.15 mM; n=27 cells, 9 patients). In cells from patients in AF, the sensitivity of Ip to both Vm and [K+]o (<i>E</i>_max=1.02±0.05 pA/pF, EC50=1.54±0.11 mM; <i>n</i>=44 cells, 9 patients) was not significantly different from that in cells from patients in SR. Within the group of patients in AF, long-term digoxin therapy (<i>n</i>=5 patients) was associated with a small, but significant, reduction in <i>E</i>_max (0.92±0.07 pA/pF) and EC₅₀ (1.35±0.15 mM) compared with non-treatment (<i>E</i>_max=1.13±0.08 pA/pF, EC₅₀=1.76±0.14 mM; P<0.05 for each, <i>n</i>=4 patients). In cells from non-digoxin-treated patients in AF, the voltage- and [K⁺]_o-sensitivity (<i>E</i>_max and EC₅₀) were similar to those in cells from patients in SR. <b>Conclusions:</b> The Na, K pump current contributes to the human atrial cell Vm, action potential shape and ERP. However, the similarity in Ip sensitivity to both [K⁺]_o and <i>V</i>_m between atrial cells from patients with and without chronic AF indicates that <i>I</i>_p is not involved in AF-induced electrophysiological remodelling in patients.

• 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: T Technology > T Technology (General); 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
• Copyright Holders: Copyright © 2003 Elsevier
• First Published: First published in Cardiovascular Research 59(3):593-602
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.

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