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

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Workman, Anthony J. and Kane, Kathleen and Rankin, Andrew 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. ISSN 0008-6363 (https://doi.org/10.1016/S0008-6363(03)00466-8)

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Abstract

Objective: To assess the contribution of the Na, K pump current (Ip) to the action potential duration (APD) and effective refractory period (ERP) in human atrial cells, and to investigate whether Ip contributes to the changes in APD and ERP associated with chronic atrial fibrillation (AF). Methods: 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). Results: In cells from patients in SR, the Ip 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, n=7 cells, 5 patients). With an elevated pipette [Na+] of 30 mM, Ip 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 μM 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; n=9 cells), confirming the K+-induced current as Ip. Ip increased linearly with increasing Vm between −120 and +60 mV (n=25 cells). Stepwise increments in [K+]o (between 0 and 10 mM) increased Ip in a concentration-dependent manner (maximum response, Emax=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 (Emax=1.02±0.05 pA/pF, EC50=1.54±0.11 mM; n=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 (n=5 patients) was associated with a small, but significant, reduction in Emax (0.92±0.07 pA/pF) and EC50 (1.35±0.15 mM) compared with non-treatment (Emax=1.13±0.08 pA/pF, EC50=1.76±0.14 mM; P<0.05 for each, n=4 patients). In cells from non-digoxin-treated patients in AF, the voltage- and [K+]o-sensitivity (Emax and EC50) were similar to those in cells from patients in SR. Conclusions: 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 Vm between atrial cells from patients with and without chronic AF indicates that Ip is not involved in AF-induced electrophysiological remodelling in patients.

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