Copyright © 2007, European Society of Cardiology
The acid-sensitive potassium channel TASK-1 in rat cardiac muscle
aInstitut für Physiologie, Universität Marburg, Deutschhausstr. 2, 35037 Marburg, Germany
bKlinik für Anästhesiologie, Universitätsklinikum Marburg, 35033 Marburg, Germany
cNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112-5000, USA
dInstitut für Physiologie, Universität Würzburg, Röntgenring 9, 97070 Würzburg, Germany
* Corresponding author. Institute of Physiology, Marburg University Deutschhausstrasse 2, 35037 Marburg, Germany. Tel.: +49 6421 2866494; fax: +49 6421 2868960. jdaut{at}staff.uni-marburg.de
Objective The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (ITASK) and its inhibition via 
1-adrenergic receptors was studied in rat ventricular cardiomyocytes.
Methods Quantitative RT-PCR experiments were carried out with mRNA from rat heart. Patch-clamp recordings were performed in isolated rat cardiomyocytes. TASK-1 and other K+ channels were expressed in Xenopus oocytes to study the pharmacological properties of a new TASK-1 channel blocker, A293.
Results TASK-1 channels were found to be strongly expressed in rat heart. Analysis of the sensitivity of various K+ channels to A293 in Xenopus oocytes showed that at low concentrations A293 was a selective blocker of TASK-1 channels. ITASK in rat cardiomyocytes was dissected by application of A293 and by extracellular acidification to pH 6.0; it had an amplitude of 
0.30 pA/pF at +30 mV. Application of 200 nM A293 increased action potential duration (APD50) by 31±3% at a stimulation rate of 4 Hz. The plausibility of the effects of A293 on APD50 was checked with a mathematical action potential model. Application of the 1-adrenergic agonist methoxamine inhibited ITASK in Xenopus oocytes co-injected with cRNA for TASK-1 and 1A-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to ITASK. This effect was abolished in the presence of the 1A-antagonist 5-methyl-urapidil.
Conclusions Our results suggest that in rat cardiomyocytes ITASK makes a substantial contribution to the outward current flowing in the plateau range of potentials and that this current component can be inhibited via 1A-adrenergic receptors.
KEYWORDS membrane currents; K channel; adrenergic agonists; action potential duration; cardiac myocytes; alpha1A adrenergic receptors
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