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

Objective: The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (I-TASK) and its inhibition via alpha 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. I-TASK in rat cardiomyocytes was dissected by application of A293 and by extracellular acidification to pH 6.0; it had an amplitude of similar to 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 APD(50) was checked with a mathematical action potential model. Application of the alpha(1)-adrenergic agonist methoxamine inhibited I-TASK in Xenopus oocytes co-injected with cRNA for TASK-1 and alpha(1A)-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to I-TASK. This effect was abolished in the presence of the alpha(1A)-antagonist 5-methyl-urapidil. Conclusions: 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 alpha(1A)-adrenergic receptors. (c) 2007 European Society of Cardiology. Published by Elsevier B.V All rights reserved.