The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Molecular Basis of Downregulation of G-Protein–Coupled Inward Rectifying K+Current (IK,ACh) in Chronic Human Atrial Fibrillation: Decrease in GIRK4 mRNA Correlates With ReducedIK,AChand Muscarinic Receptor–Mediated Shortening of Action Potentials
Abstract
BackgroundClinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K+current (IK,ACh) contribute to chronic AF. Methods and ResultsIn the present study, we used electrophysiological recordings and competitive reverse-transcription polymerase chain reaction to study changes in IK,ACh and the level of the IK,ACh GIRK4 subunit in isolated human atrial myocytes and the atrial tissue of 39 patients with sinus rhythm and 24 patients with chronic AF. The density of IK,ACh was ≈50% smaller in myocytes from patients with AF compared with those in sinus rhythm, and this was accompanied by decreased levels of GIRK4 mRNA. The current density of the inward rectifying K+current (IK1) was 2-fold larger during AF than in sinus rhythm, in correspondence with an increase in Kir2.1 mRNA. The larger IK1 in AF is consistent with more negative membrane potentials in right atrial trabeculae from AF patients. Moreover, action potential duration was reduced in AF, and the action potential shortening produced by muscarinic receptor stimulation was attenuated, indicating that the changes of IK1 and IK,ACh were functionally relevant. ConclusionsChronic human AF induces transcriptionally mediated upregulation of IK1 but downregulation of IK,ACh and attenuates the muscarinic receptor–mediated shortening of atrial action potentials. This suggests that atrial myocytes adapt to a chronically high rate by downregulating IK,ACh to counteract the shortening of the atrial effective refractory period due to electrical remodeling.
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Association of a human G-protein β3 subunit variant with hypertension
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Ionic mechanisms of electrical remodeling in human atrial fibrillation
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Atrial L-Type Ca 2+ Currents and Human Atrial Fibrillation
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Outward K + Current Densities and Kv1.5 Expression Are Reduced in Chronic Human Atrial Fibrillation
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G Protein Regulation of Potassium Ion Channels
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Catheter Ablation of Cardiac Autonomic Nerves for Prevention of Vagal Atrial Fibrillation
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Cited by
Pathophysiological mechanisms of atrial fibrillation: a translational appraisal
Schotten, U., Verheule, S., Kirchhof, P., & Goette, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00031.2009 · Cited by 1,273
Atrial Remodeling and Atrial Fibrillation: Mechanisms and Implications
Nattel, S., Burstein, B., & Dobrev, D. (2008) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.107.754564 · Cited by 1,124
Self-citationGoette, A., Kalman, J. M., Aguinaga, L., Akar, J., Cabrera, J. A., Chen, S. A., Chugh, S. S., Corradi, D., D’Avila, A., Dobrev, D., et al. (2017) · Heart Rhythm · doi:10.1016/j.hrthm.2016.05.028 · Cited by 771
Self-citationHeijman, J., Voigt, N., Nattel, S., & Dobrev, D. (2014) · Circulation Research · doi:10.1161/circresaha.114.302226 · Cited by 677
Self-citationVoigt, N., Li, N., Wang, Q., Wang, W., Trafford, A. W., Abu-Taha, I., Sun, Q., Wieland, T., Ravens, U., Nattel, S., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.067306 · Cited by 624
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Metadata
- Authors
- Dobrev, D., Graf, E., Wettwer, E., Himmel, H. M., Hála, O., Doerfel, C., Christ, T., Schüler, S., & Ravens, U.
- Venue
- Circulation
- Published
- 2001-11-20
- Volume
- 104
- Issue
- 21
- Pages
- 2551-2557
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2107213822
- Cited by
- 320
- References
- 23
- FWCI
- 9.30
- Type
- journal article
- Language
- en
- Open access
- closed
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- Dobrev, D., Graf, E., Wettwer, E., Himmel, H. M., Hála, O., Doerfel, C., Christ, T., Schüler, S., & Ravens, U. (2001). Molecular Basis of Downregulation of G-Protein–Coupled Inward Rectifying K+Current (IK,ACh) in Chronic Human Atrial Fibrillation: Decrease in GIRK4 mRNA Correlates With ReducedIK,AChand Muscarinic Receptor–Mediated Shortening of Action Potentials. Circulation. https://doi.org/10.1161/hc4601.099466
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