Anti-KCNQ1 K+ channel autoantibodies increase IKs current and are associated with QT interval shortening in dilated cardiomyopathy
Autoimmune-associated proarrhythmia in dilated cardiomyopathy (DCM) is poorly understood. Given the significance of KCNQ1 potassium channels in heart rhythm disorders, we hypothesized that circulating anti-KCNQ1 autoantibodies directly modulate cardiac electrophysiology in DCM patients. The purpose...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2013
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| In: |
Cardiovascular research
Year: 2013, Volume: 98, Issue: 3, Pages: 496-503 |
| ISSN: | 1755-3245 |
| DOI: | 10.1093/cvr/cvt046 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/cvr/cvt046
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| Author Notes: | Jin Li, Claudia Seyler, Felix Wiedmann, Constanze Schmidt, Patrick A. Schweizer, Rüdiger Becker, Hugo A. Katus, and Dierk Thomas |
| Summary: | Autoimmune-associated proarrhythmia in dilated cardiomyopathy (DCM) is poorly understood. Given the significance of KCNQ1 potassium channels in heart rhythm disorders, we hypothesized that circulating anti-KCNQ1 autoantibodies directly modulate cardiac electrophysiology in DCM patients. The purpose of this pilot study was to characterize ion channel autoantibodies in DCM targeting the cardiac repolarizing K+ current, IKs, and the underlying KCNQ1 potassium channel.One hundred and fifty DCM patients were screened for anti-KCNQ1 autoantibodies using an enzyme-linked immunosorbent assay. Autoantibodies targeting the extracellular pore domain of the KCNQ1 channel were detected in 6% of study patients. Seropositive individuals exhibited significantly shorter corrected QT intervals when compared with seronegative patients (371 ± 39.9 ms vs. 408 ± 47.9 ms; P = 0.036). There was no difference in clinical severity of heart failure between groups. The functional significance of anti-KCNQ1 antibodies was determined in human embryonic kidney 293 cells expressing KCNQ1/KCNE1 using the whole-cell patch clamp technique. IKs recordings demonstrated a 2.7-fold increase in mean current density on exposure to patients' sera containing anti-KCNQ1 antibodies in contrast to seronegative controls (8.74 ± 1.44 pA/pF vs. 3.26 ± 0.36 pA/pF; P = 0.003). IKs enhancement was not associated with increased KCNQ1 protein levels or altered cell surface expression of the channel.Anti-KCNQ1 autoantibodies found in a subgroup of DCM patients are associated with QT interval shortening and increased IKs current. |
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| Item Description: | Online publish-ahead-of-print 27 February 2013 Im Titel ist das Pluszeichen "+" hochgestellt und nach dem Buchstabe "I" ist "Ks" tiefgestellt Gesehen am 21.02.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1755-3245 |
| DOI: | 10.1093/cvr/cvt046 |