Channelpedia

PubMed 25655935


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNK3 , KCNK9



Title: TASK-1 and TASK-3 may form heterodimers in human atrial cardiomyocytes.

Authors: Susanne Rinné, Aytug K Kiper, Günter Schlichthörl, Sven Dittmann, Michael F Netter, Sven H Limberg, Nicole Silbernagel, Marylou Zuzarte, Rainer Moosdorf, Hinnerk Wulf, Eric Schulze-Bahr, Caroline Rolfes, Niels Decher

Journal, date & volume: J. Mol. Cell. Cardiol., 2015 Apr , 81, 71-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25655935


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.