© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation
aDepartment of Pharmacology and Toxicology, Carl Gustav Carus Medical School, Dresden University of Technology, Dresden, Germany
bCardiovascular Centre, Carl Gustav Carus Medical School, Dresden University of Technology, Dresden, Germany
dobrev{at}rcs.urz.tu-dresden.de
* Corresponding author. Department of Pharmacology and Toxicology, TU Dresden, Fetscher Str. 74, D-01307 Dresden, Germany. Tel.: +49-351-458-6279; fax: +49-351-458-6315
Objective: We showed recently that the 825T allele of the G-protein β3-subunit C825T polymorphism is associated with large inward rectifier K+ currents IK1 but low acetylcholine-activated K+ current IK,ACh amplitudes. During chronic atrial fibrillation (AF), IK1 and IK,ACh current densities were increased when compared to sinus rhythm (SR). It is unknown whether chronic AF and Gβ3 gene status are independent contributors to atrial K+ current activity. We measured IK1 and IK,ACh in tissue from AF patients with different Gβ3 genotypes and assessed the relation between the IK1 and IK,ACh amplitudes and the incidence of postoperative AF. Methods: We measured the amplitudes of IK1 and IK,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 Gβ3 gene status of the patients was determined by PCR and restriction analysis. Results: At –100 mV, the amplitude of IK1 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 IK,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 Gβ3 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 IK1 but down-regulation of IK,ACh in chronic AF which are independent of Gβ3 gene status. Atrial myocytes from patients who are in SR but later develop postoperative AF have no manifestation of altered IK1 and IK,ACh at the time of cardiac surgery. Our results suggest that the AF-related changes of IK1 and IK,ACh may be a consequence of or a contributory factor to chronic AF.
KEYWORDS Atrial function; Gene expression; K-channel
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