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

Objective: To assess the contribution of the Na, K pump current (I-p) to the action potential duration (APD) and effective refractory period (ERP) in human atrial cells, and to investigate whether I-p 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 I-p blocker, ouabain (10 muM) significantly depolarised the membrane potential, V-m, 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, 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; n=9 cells), confirming the K+-induced current as I-p. I-p increased linearly with increasing V-m between -120 and +60 mV (n=25 cells). Stepwise increments in [K+](o) (between 0 and 10 mM) increased I-p in a concentration-dependent manner (maximum response, E-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 I-p to both V-m and [K+](o) (E-max = 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 E-max (0.92+/-0.07 pA/pF) and EC50 (1.35+/-0.15 mM) compared with non-treatment (E-max = 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 (E-max and EC50) were similar to those in cells from patients in SR. Conclusions: The Na, K pump current contributes to the human atrial cell,, action potential shape and ERP. However, the similarity in I-p sensitivity to both [K+](o) and V-m between atrial cells from patients with and without chronic AF indicates that I-p is not involved in AF-induced electrophysiological remodelling in patients. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.