title: TASK-1 and TASK-3 may form heterodimers in human atrial cardiomyocytes.
abstract: TASK-1 channels have emerged as promising drug targets against atrial fibrillation, the most common arrhythmia in the elderly. While TASK-3, the closest relative of TASK-1, was previously not described in cardiac tissue, we found a very prominent expression of TASK-3 in right human auricles. Immunocytochemistry experiments of human right auricular cardiomyocytes showed that TASK-3 is primarily localized at the plasma membrane. Single-channel recordings of right human auricles in the cell-attached mode, using divalent-cation-free solutions, revealed a TASK-1-like channel with a single-channel conductance of about 30pS. While homomeric TASK-3 channels were not found, we observed an intermediate single-channel conductance of about 55pS, possibly reflecting the heteromeric channel formed by TASK-1 and TASK-3. Subsequent experiments with TASK-1/TASK-3 tandem channels or with co-expressed TASK-1 and TASK-3 channels in HEK293 cells or Xenopus oocytes, supported that the 55pS channels observed in right auricles have electrophysiological characteristics of TASK-1/TASK-3 heteromers. In addition, co-expression experiments and single-channel recordings suggest that heteromeric TASK-1/TASK-3 channels have a predominant surface expression and a reduced affinity for TASK-1 blockers. In summary, the evidence for heteromeric TASK-1/TASK-3 channel complexes together with an altered pharmacologic response to TASK-1 blockers in vitro is likely to have further impact for studies isolating ITASK-1 from cardiomyocytes and for the development of drugs specifically targeting TASK-1 in atrial fibrillation treatment.
authors: Institut für Physiologie und Pathophysiologie, Abteilung vegetative Physiologie, Universität Marburg, 35037 Marburg, Germany.
authors: Susanne
authors: S
authors: Rinné
authors: Institut für Physiologie und Pathophysiologie, Abteilung vegetative Physiologie, Universität Marburg, 35037 Marburg, Germany.
authors: Aytug K
authors: AK
authors: Kiper
authors: Institut für Physiologie und Pathophysiologie, Abteilung kardiovaskuläre Zellphysiologie, Universität Marburg, 35037 Marburg, Germany.
authors: Günter
authors: G
authors: Schlichthörl
authors: Institut für Genetik von Herzerkrankungen (IfGH), Department für Kardiologie und Angiologie, Universitätsklinikum Münster, Münster, Germany.
authors: Sven
authors: S
authors: Dittmann
authors: Institut für Physiologie und Pathophysiologie, Abteilung vegetative Physiologie, Universität Marburg, 35037 Marburg, Germany.
authors: Michael F
authors: MF
authors: Netter
authors: Klinik für Anästhesie und Intensivtherapie, Philipps-Universität Marburg, 35033 Marburg, Germany.
authors: Sven H
authors: SH
authors: Limberg
authors: Institut für Physiologie und Pathophysiologie, Abteilung vegetative Physiologie, Universität Marburg, 35037 Marburg, Germany.
authors: Nicole
authors: N
authors: Silbernagel
authors: Institut für Physiologie und Pathophysiologie, Abteilung kardiovaskuläre Zellphysiologie, Universität Marburg, 35037 Marburg, Germany.
authors: Marylou
authors: M
authors: Zuzarte
authors: Klinik für Herz- und thorakale Gefäßchirurgie, Universitätsklinikum Giessen und Marburg, Standort Marburg, 35033 Marburg, Germany.
authors: Rainer
authors: R
authors: Moosdorf
authors: Klinik für Anästhesie und Intensivtherapie, Philipps-Universität Marburg, 35033 Marburg, Germany.
authors: Hinnerk
authors: H
authors: Wulf
authors: Institut für Genetik von Herzerkrankungen (IfGH), Department für Kardiologie und Angiologie, Universitätsklinikum Münster, Münster, Germany.
authors: Eric
authors: E
authors: Schulze-Bahr
authors: Klinik für Anästhesie und Intensivtherapie, Philipps-Universität Marburg, 35033 Marburg, Germany.
authors: Caroline
authors: C
authors: Rolfes
authors: Institut für Physiologie und Pathophysiologie, Abteilung vegetative Physiologie, Universität Marburg, 35037 Marburg, Germany. Electronic address: decher@staff.uni-marburg.de.
authors: Niels
authors: N
authors: Decher
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D001549:Benzamides / Q000494:pharmacology; D044482:Benzeneacetamides / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D014982:Xenopus laevis; D062367:ortho-Aminobenzoates / Q000494:pharmacology
chemical_list: C577579:2-(butane-1-sulfonylamino)-N-(1-(6-methoxypyridin-3-yl)propyl)benzamide; C558924:A 1899; D001549:Benzamides; D044482:Benzeneacetamides; C498655:KCNK9 protein, human; D009419:Nerve Tissue Proteins; D026902:Potassium Channel Blockers; D024683:Potassium Channels, Tandem Pore Domain; D011994:Recombinant Proteins; D013449:Sulfonamides; D062367:ortho-Aminobenzoates; C420132:potassium channel subfamily K member 3
keywords: Atrial fibrillation; Cardiomyocytes; Heteromers; K(2P) channel; Right human auricles; TASK