Signalling between G-protein-coupled receptors and TASK1 channels

This editorial refers to ‘Inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C’ by J. Schiekel et al ., pp. 97–105, this issue. The superfamily of two pore-domain K+ (K2P) channels has a least 15 members,1 of which mainly TASK1 is expressed in cardiac myocytes. TASK1 gating is voltage independent, but the channel is acid sensitive, being activated by alkalotic conditions. Ion currents carried by TASK1 likely contribute to the cardiac action potential duration (APD), and pharmacological inhibition of TASK1 lengthens the APD2,3 while TASK1 knock-out animals display a long QT on the electrocardiogram.4,5 Interest in TASK1 channels has been mounting, because their activity in various cell types seems critical for several physiological processes while their changed expression and/or function may underlie many disease conditions. The channels are potential targets for diverse therapeutic actions, including antiarrhythmic, antihypertensive, antiepileptic, and antidepressive treatments as well as analgesia and inhalation anaesthesia.6 Therefore, identifying the signalling pathways involved in their regulation is important. Newly available investigation tools, such as those used in the study of Schiekel et al. 7 published in the current issue of Cardiovascular Research , allow one to investigate the signalling pathways for the regulation of TASK1 in intact cells while monitoring cell membrane lipid metabolism.A well-recognized regulation of TASK1 channels is their inhibition by receptors coupled to the G-protein Gp, which is linked to membrane phospholipid breakdown via the activation of phospholipase C (PLC). Neurotransmitters such as norepinephrine (acting on α–adrenergic receptors), hormones such angiotensin or endothelin-1, and other agonists (e.g. platelet-activating factor, PAF) reduce TASK1 ion currents.1 The signalling pathway linking Gp activation to TASK1 inhibition has been a source of controversy, given variable and inconsistent results …