The acid-sensitive potassium channel TASK-1 in rat cardiac muscle

• Published in: Cardiovascular research 2007-07, Vol.75 (1), p.59-68
• Main Authors: PUTZKE, Caroline, WEMHÖNER, Konstantin, PREISIG-MÜLLER, Regina, DAUT, Jürgen, DECHER, Niels, SACHSE, Frank B, RINNE, Susanne, SCHLICHTHÖRL, Günter, XIAN TAO LI, JAE, Lucas, ECKHARDT, Ines, WISCHMEYER, Erhard, WULF, Hinnerk
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Cardiology. Vascular system; Computer Simulation; Hydrogen-Ion Concentration; Medical sciences; Methoxamine - pharmacology; Models, Cardiovascular; Myocardium - metabolism; Oocytes - metabolism; Patch-Clamp Techniques; Piperazines - pharmacology; Potassium Channels, Tandem Pore Domain - antagonists & inhibitors; Potassium Channels, Tandem Pore Domain - genetics; Potassium Channels, Tandem Pore Domain - metabolism; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Transfection - methods; Xenopus laevis
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2007.02.025

The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (I(TASK)) and its inhibition via alpha1-adrenergic receptors was studied in rat ventricular cardiomyocytes. 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. 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. I(TASK) in rat cardiomyocytes was dissected by application of A293 and by extracellular acidification to pH 6.0; it had an amplitude of approximately 0.30 pA/pF at +30 mV. Application of 200 nM A293 increased action potential duration (APD(50)) 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 alpha1-adrenergic agonist methoxamine inhibited I(TASK) in Xenopus oocytes co-injected with cRNA for TASK-1 and alpha1A-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to I(TASK). This effect was abolished in the presence of the alpha1A-antagonist 5-methyl-urapidil. Our results suggest that in rat cardiomyocytes I(TASK) makes a substantial contribution to the outward current flowing in the plateau range of potentials and that this current component can be inhibited via alpha1A-adrenergic receptors.