Copyright © 2005, European Society of Cardiology
The stretch-activated potassium channel TREK-1 in rat cardiac ventricular muscle
aInstitut für Physiologie, Universität Marburg, Deutschhausstr. 2, 35037 Marburg, Germany
bJulius-Bernstein-Institut für Physiologie, Universität Halle, Magdeburger Str. 6, 06097 Halle, Germany
cKlinik für Anästhesie, Universitätsklinikum Giessen-Marburg, Baldingerstr., 35033 Marburg, Germany
* Corresponding author. Institute of Physiology Marburg University Deutschhausstrasse 2, 35037 Marburg, Germany. Tel.: +49 6421 2866494; fax: +49 6421 2868960. Email address: jdaut{at}staff.uni-marburg.de
Objective: The biophysical properties and the regulation of the two-pore-domain potassium channel TREK-1 were studied in rat cardiomyocytes.
Methods: RT-PCR, immunohistochemistry and patch-clamp recording were performed in isolated rat ventricular cardiomyocytes. In some whole-cell-clamp experiments the myocytes were mechanically stretched using a glass stylus.
Results: We found strong expression of a splice variant of TREK-1 in rat heart. Immunohistochemistry with antibodies against TREK-1 showed localization of the channel in longitudinal stripes at the external surface membrane of cardiomyocytes. When the cardiomyocytes were mechanically stretched, an outwardly rectifying K+ current component could be detected in whole-cell recordings. In single-channel recordings with symmetrical high K+ solution, two TREK-like channels with ‘flickery-burst’ kinetics were found: a ‘large conductance’ K+ channel (132 ± 5 pS at positive potentials) and a novel ‘low-conductance’ channel (41 ± 5 pS at positive potentials). The low-conductance channel could be activated by negative pressure in inside-out patches, positive pressure in outside-out patches, intracellular acidification and application of arachidonic acid. Its open probability was strongly increased by depolarization, due to decreased duration of gaps between bursts. The biophysical properties of the two cardiac TREK-like channels were similar to those of TREK-1 channels expressed in HEK293 cells, which both displayed low- and high-conductance modes.
Conclusions: Our results suggest that the two TREK-like channels found in rat cardiomyocytes may reflect two different operating modes of TREK-1. The novel low-conductance channels described here may represent the major operating mode of TREK-1. The current flowing through mechanogated TREK-1 channels may serve to counterbalance the inward current flowing through stretch-activated non-selective cation channels during the filling phase of the cardiac cycle and thus to prevent the occurrence of ventricular extrasystoles.
KEYWORDS K-channel; Arrhythmia (mechanisms); Stretch; Stretch-activated K-channels; K2P channels
Time for primary review 14 days
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