Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation

Objective: We showed recently that the 825T allele of the G-protein beta3-subunit C825T polymorphism is associated with large inward rectifier K+ currents I-KI but low acetylcholine-activated K+ current I-K,I-ACh amplitudes. During chronic atrial fibrillation (AF). I-KI and I-K,I-ACh current densities were increased when compared to sinus rhythm (SR). It is unknown whether chronic AF and Gbeta3 gene status are independent contributors to atrial K+ current activity. We measured I-KI and I-K,I-ACh in tissue from AF patients with different Gbeta3 genotypes and assessed the relation between the I-KI and I-K,I-Ach amplitudes and the incidence of postoperative AF. Methods: We measured the amplitudes of I-KI and I-K,I-ACh in atrial myocytes from 26 patients with sinus rhythm (SR) and from 16 patients with chronic AF (>6 months). The K+ currents were measured with standard patch-clamp techniques. The Gbeta3 gene status of the patients was determined by PCR and restriction analysis. Results: At -100 mV, the amplitude of I-KI was larger in AF (10.9+/-1.0 pA/pF, n=49/16. cells/patients) than in SR (6.3+/-0.6 pA/pF, n=68/26, P<0.05), whereas the amplitude of I-K,I-ACh was smaller in chronic AF (2.9+/-0.7 pA/pF, n=49/16) than in SR (6.3+/-0.7 pA/pF, n=68/26, P<0.05). These changes were independent of the patient Gbeta3 gene status. Eight patients out of 26 in the SR group (31%) developed postoperative AF. When analysed based on incidence of postoperative AF, current amplitudes did not differ significantly. Conclusion: We provide evidence for up-regulation of I-KI but down-regulation of I-K,I-ACh in chronic AF which are independent of Gbeta3 gene status. Atrial myocytes from patients who are in SR but later develop postoperative AF have no manifestation of altered I-KI and I-K,I-ACh at the time of cardiac surgery. Our results suggest that the AF-related changes of I-KI and I-K,I-ACh may be a consequence of or a contributory factor to chronic AF. (C) 2002 Elsevier Science B.V. All rights reserved.