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Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation
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| Veröffentlicht in: | Circulation 132(2015), 2, Seite 82-92 |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , |
| Titel: | Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation/ Constanze Schmidt, Felix Wiedmann, Niels Voigt, Xiao-Bo Zhou, Jordi Heijman, Siegfried Lang, Virginia Albert, Stefan Kallenberger, Arjang Ruhparwar, Gábor Szabó, Klaus Kallenbach, Matthias Karck, Martin Borggrefe, Peter Biliczki, Joachim R. Ehrlich, István Baczkó, Patrick Lugenbiel, Patrick A. Schweizer, Birgit C. Donner, Hugo A. Katus, Dobromir Dobrev, Dierk Thomas |
| Format: | E-Book-Kapitel |
| Sprache: | Englisch |
| veröffentlicht: |
14 July 2015
|
| Gesamtaufnahme: |
: Circulation, 132(2015), 2, Seite 82-92
, volume:132 |
| Schlagwörter: | |
| Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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| 245 | 1 | 0 | |a Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation |c Constanze Schmidt, Felix Wiedmann, Niels Voigt, Xiao-Bo Zhou, Jordi Heijman, Siegfried Lang, Virginia Albert, Stefan Kallenberger, Arjang Ruhparwar, Gábor Szabó, Klaus Kallenbach, Matthias Karck, Martin Borggrefe, Peter Biliczki, Joachim R. Ehrlich, István Baczkó, Patrick Lugenbiel, Patrick A. Schweizer, Birgit C. Donner, Hugo A. Katus, Dobromir Dobrev, Dierk Thomas |
| 246 | 3 | 3 | |a Upregulation of K 2P 3.1 K + current causes action potential shortening in patients with chronic atrial fibrillation |
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| 520 | |a Background-Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K2P3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K2P) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Methods and Results—Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K2P3.1 subunits exhibited predominantly atrial expression, and atrial K2P3.1 transcript levels were highest among functional K2P channels. K2P3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K2P3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K2P3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Conclusions—Enhancement of atrium-selective K2P3.1 currents contributes to APD shortening in patients with chronic AF, and K2P3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K2P3.1 as a novel drug target for mechanism-based AF therapy. | ||
| 650 | 4 | |a arrhythmias, cardiac | |
| 650 | 4 | |a atrial fibrillation | |
| 650 | 4 | |a electrophysiology | |
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| 900 | |a Schmidt, Constanze Viola Kathrin | ||
| 900 | |a Schmidt, C. | ||
| 900 | |a Karck, M. | ||
| 900 | |a Wiedmann, Felix | ||
| 900 | |a Wiedmann, F. | ||
| 900 | |a Kallenbach, K. | ||
| 900 | |a Borggrefe, M. | ||
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| 900 | |a Katus, Hugo S. | ||
| 900 | |a Katus, H. A. | ||
| 900 | |a Katus, Hugo Albert | ||
| 900 | |a Lang, S. | ||
| 900 | |a Zhou, Xiaobo | ||
| 900 | |a Zhou, X. | ||
| 900 | |a Kallenberger, Stefan Matthias | ||
| 900 | |a Kallenberger, Stefan | ||
| 900 | |a Schweizer, Patrick | ||
| 900 | |a Schweizer, Patrick A. | ||
| 900 | |a Schweizer, P. A. | ||
| 900 | |a Thomas, D. | ||
| 900 | |a Ruhpawar, Arjang | ||
| 900 | |a Ruhparwar, A. | ||
| 900 | |a Voigt, Wolfgang Niels | ||
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| author | Schmidt, Constanze, Wiedmann, Felix Tobias, Voigt, Niels, Zhou, Xiao-Bo, Lang, Siegfried, Albert, Virginia, Kallenberger, Stefan M., Ruhparwar, Arjang, Szabó, Gábor, Kallenbach, Klaus, Karck, Matthias, Borggrefe, Martin, Lugenbiel, Patrick, Schweizer, Patrick Alexander, Katus, Hugo, Dobrev, Dobromir, Thomas, Dierk |
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| contents | Background-Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K2P3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K2P) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Methods and Results—Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K2P3.1 subunits exhibited predominantly atrial expression, and atrial K2P3.1 transcript levels were highest among functional K2P channels. K2P3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K2P3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K2P3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Conclusions—Enhancement of atrium-selective K2P3.1 currents contributes to APD shortening in patients with chronic AF, and K2P3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K2P3.1 as a novel drug target for mechanism-based AF therapy. |
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| spelling | Schmidt, Constanze VerfasserIn (DE-588)1055852174 (DE-627)792733142 (DE-576)411903721 aut, Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation Constanze Schmidt, Felix Wiedmann, Niels Voigt, Xiao-Bo Zhou, Jordi Heijman, Siegfried Lang, Virginia Albert, Stefan Kallenberger, Arjang Ruhparwar, Gábor Szabó, Klaus Kallenbach, Matthias Karck, Martin Borggrefe, Peter Biliczki, Joachim R. Ehrlich, István Baczkó, Patrick Lugenbiel, Patrick A. Schweizer, Birgit C. Donner, Hugo A. Katus, Dobromir Dobrev, Dierk Thomas, Upregulation of K 2P 3.1 K + current causes action potential shortening in patients with chronic atrial fibrillation, 14 July 2015, 11, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 24.02.2017, Im Titel ist "2P" tiefgestellt, "+" hochgestellt, Background-Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K2P3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K2P) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Methods and Results—Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K2P3.1 subunits exhibited predominantly atrial expression, and atrial K2P3.1 transcript levels were highest among functional K2P channels. K2P3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K2P3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K2P3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Conclusions—Enhancement of atrium-selective K2P3.1 currents contributes to APD shortening in patients with chronic AF, and K2P3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K2P3.1 as a novel drug target for mechanism-based AF therapy., arrhythmias, cardiac, atrial fibrillation, electrophysiology, Wiedmann, Felix Tobias 1987- VerfasserIn (DE-588)1055852441 (DE-627)792733479 (DE-576)411904159 aut, Voigt, Niels 1981- VerfasserIn (DE-588)133880184 (DE-627)557868572 (DE-576)276614593 aut, Zhou, Xiao-Bo 1958- VerfasserIn (DE-588)1117113744 (DE-627)871032457 (DE-576)478766742 aut, Lang, Siegfried 1955- VerfasserIn (DE-588)1026112613 (DE-627)726109290 (DE-576)371365473 aut, Albert, Virginia VerfasserIn (DE-588)1126283681 (DE-627)881224065 (DE-576)484478532 aut, Kallenberger, Stefan M. 1982- VerfasserIn (DE-588)104751074X (DE-627)778493245 (DE-576)401124517 aut, Ruhparwar, Arjang VerfasserIn (DE-588)138079021 (DE-627)599042591 (DE-576)306325926 aut, Szabó, Gábor 1969- VerfasserIn (DE-588)1022955152 (DE-627)717338681 (DE-576)366215485 aut, Kallenbach, Klaus 1965- VerfasserIn (DE-588)115399364 (DE-627)077223926 (DE-576)289859875 aut, Karck, Matthias 1961- VerfasserIn (DE-588)130833525 (DE-627)505909340 (DE-576)298366169 aut, Borggrefe, Martin VerfasserIn (DE-588)1025920546 (DE-627)725574232 (DE-576)370913426 aut, Lugenbiel, Patrick 1982- VerfasserIn (DE-588)137855710 (DE-627)696120062 (DE-576)305349414 aut, Schweizer, Patrick Alexander 1976- VerfasserIn (DE-588)129886254 (DE-627)48277987X (DE-576)297887130 aut, Katus, Hugo 1951- VerfasserIn (DE-588)108916618 (DE-627)577155040 (DE-576)289625076 aut, Dobrev, Dobromir 1964- VerfasserIn (DE-588)1035228718 (DE-627)746999127 (DE-576)382840070 aut, Thomas, Dierk 1974- VerfasserIn (DE-588)123896258 (DE-627)706465601 (DE-576)29393164X aut, Enthalten in Circulation Philadelphia, Pa. : Lippincott, Williams & Wilkins, 1950 132(2015), 2, Seite 82-92 Online-Ressource (DE-627)265784670 (DE-600)1466401-X (DE-576)074891189 1524-4539 nnns, volume:132 year:2015 number:2 pages:82-92 extent:11, http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012657 Verlag Resolving-System kostenfrei Volltext, http://circ.ahajournals.org/content/132/2/82 Verlag kostenfrei Volltext, http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012657 LFER, LFER 2017-04-13T00:00:00Z |
| spellingShingle | Schmidt, Constanze, Wiedmann, Felix Tobias, Voigt, Niels, Zhou, Xiao-Bo, Lang, Siegfried, Albert, Virginia, Kallenberger, Stefan M., Ruhparwar, Arjang, Szabó, Gábor, Kallenbach, Klaus, Karck, Matthias, Borggrefe, Martin, Lugenbiel, Patrick, Schweizer, Patrick Alexander, Katus, Hugo, Dobrev, Dobromir, Thomas, Dierk, Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation, Background-Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K2P3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K2P) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Methods and Results—Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K2P3.1 subunits exhibited predominantly atrial expression, and atrial K2P3.1 transcript levels were highest among functional K2P channels. K2P3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K2P3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K2P3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Conclusions—Enhancement of atrium-selective K2P3.1 currents contributes to APD shortening in patients with chronic AF, and K2P3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K2P3.1 as a novel drug target for mechanism-based AF therapy., arrhythmias, cardiac, atrial fibrillation, electrophysiology |
| swb_id_str | 484478621 |
| title | Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation |
| title_alt | Upregulation of K 2P 3.1 K + current causes action potential shortening in patients with chronic atrial fibrillation |
| title_auth | Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation |
| title_full | Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation Constanze Schmidt, Felix Wiedmann, Niels Voigt, Xiao-Bo Zhou, Jordi Heijman, Siegfried Lang, Virginia Albert, Stefan Kallenberger, Arjang Ruhparwar, Gábor Szabó, Klaus Kallenbach, Matthias Karck, Martin Borggrefe, Peter Biliczki, Joachim R. Ehrlich, István Baczkó, Patrick Lugenbiel, Patrick A. Schweizer, Birgit C. Donner, Hugo A. Katus, Dobromir Dobrev, Dierk Thomas |
| title_fullStr | Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation Constanze Schmidt, Felix Wiedmann, Niels Voigt, Xiao-Bo Zhou, Jordi Heijman, Siegfried Lang, Virginia Albert, Stefan Kallenberger, Arjang Ruhparwar, Gábor Szabó, Klaus Kallenbach, Matthias Karck, Martin Borggrefe, Peter Biliczki, Joachim R. Ehrlich, István Baczkó, Patrick Lugenbiel, Patrick A. Schweizer, Birgit C. Donner, Hugo A. Katus, Dobromir Dobrev, Dierk Thomas |
| title_full_unstemmed | Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation Constanze Schmidt, Felix Wiedmann, Niels Voigt, Xiao-Bo Zhou, Jordi Heijman, Siegfried Lang, Virginia Albert, Stefan Kallenberger, Arjang Ruhparwar, Gábor Szabó, Klaus Kallenbach, Matthias Karck, Martin Borggrefe, Peter Biliczki, Joachim R. Ehrlich, István Baczkó, Patrick Lugenbiel, Patrick A. Schweizer, Birgit C. Donner, Hugo A. Katus, Dobromir Dobrev, Dierk Thomas |
| title_in_hierarchy | Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation / Constanze Schmidt, Felix Wiedmann, Niels Voigt, Xiao-Bo Zhou, Jordi Heijman, Siegfried Lang, Virginia Albert, Stefan Kallenberger, Arjang Ruhparwar, Gábor Szabó, Klaus Kallenbach, Matthias Karck, Martin Borggrefe, Peter Biliczki, Joachim R. Ehrlich, István Baczkó, Patrick Lugenbiel, Patrick A. Schweizer, Birgit C. Donner, Hugo A. Katus, Dobromir Dobrev, Dierk Thomas, |
| title_short | Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation |
| title_sort | upregulation of k2p3 1 k current causes action potential shortening in patients with chronic atrial fibrillation |
| topic | arrhythmias, cardiac, atrial fibrillation, electrophysiology |
| topic_facet | arrhythmias, cardiac, atrial fibrillation, electrophysiology |
| url | http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012657, http://circ.ahajournals.org/content/132/2/82 |