Objective The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (I_TASK) and its inhibition via α₁-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 ∼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 α₁-adrenergic agonist methoxamine inhibited I_TASK in Xenopus oocytes co-injected with cRNA for TASK-1 and α_1A-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to I_TASK. This effect was abolished in the presence of the α_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 α_1A-adrenergic receptors.