The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension.

Background And Purpose: Pulmonary arterial hypertension (PAH) is a progressive disease in which chronic membrane potential (E) depolarisation of the pulmonary arterial smooth muscle cells (PASMCs) causes calcium overload, a key pathological alteration. Under resting conditions, the negative E is mainly set by two pore domain potassium (K) channels, of which the TASK-1 has been extensively investigated.

Experimental Approach: Ion channel currents and membrane potential of primary cultured human(h) PASMCs were measured using the voltage- and current clamp methods.

The yellow brick road to nuclear membrane mechanotransduction.

The nuclear membrane may function as a mechanosensory surface alongside the plasma membrane. In this Review, we discuss how this idea emerged, where it currently stands, and point out possible implications, without any claim of comprehensiveness.

Negative Influence by the Force: Mechanically Induced Hyperpolarization via K Background Potassium Channels.

The two-pore domain K subunits form background (leak) potassium channels, which are characterized by constitutive, although not necessarily constant activity, at all membrane potential values. Among the fifteen pore-forming K subunits encoded by the KCNK genes, the three members of the TREK subfamily, TREK-1, TREK-2, and TRAAK are mechanosensitive ion channels. Mechanically induced opening of these channels generally results in outward K current under physiological conditions, with consequent hyperpolarization and inhibition of membrane potential-dependent cellular functions.

TRESK background potassium channel modifies the TRPV1-mediated nociceptor excitability in sensory neurons.

Background: TWIK-related spinal cord potassium channel (TRESK) background potassium channels have a key role in controlling resting membrane potential and excitability of sensory neurons. A frameshift mutation leading to complete loss of TRESK function has been identified in members of a family suffering from migraine with aura. In the present study, we examined the role of TRESK channels on nociceptor function in mice.

Endothelial Dysfunction Following Enhanced TMEM16A Activity in Human Pulmonary Arteries.

Endothelial dysfunction is one of the hallmarks of different vascular diseases, including pulmonary arterial hypertension (PAH). Ion channelome changes have long been connected to vascular remodeling in PAH, yet only recently has the focus shifted towards Ca-activated Cl channels (CaCC). The most prominent member of the CaCC TMEM16A has been shown to contribute to the pathogenesis of idiopathic PAH (IPAH) in pulmonary arterial smooth muscle cells, however its role in the homeostasis of healthy human pulmonary arterial endothelial cells (PAECs) and in the development of endothelial dysfunction remains underrepresented.

TRESK and TREK-2 two-pore-domain potassium channel subunits form functional heterodimers in primary somatosensory neurons.

Two-pore-domain potassium channels (K) are the major determinants of the background potassium conductance. They play a crucial role in setting the resting membrane potential and regulating cellular excitability. These channels form homodimers; however, a few examples of heterodimerization have also been reported.

Targeting TMEM16A to reverse vasoconstriction and remodelling in idiopathic pulmonary arterial hypertension.

Our systematic analysis of anion channels and transporters in idiopathic pulmonary arterial hypertension (IPAH) showed marked upregulation of the Cl channel TMEM16A gene. We hypothesised that TMEM16A overexpression might represent a novel vicious circle in the molecular pathways causing pulmonary arterial hypertension (PAH).We investigated healthy donor lungs (n=40) and recipient lungs with IPAH (n=38) for the expression of anion channel and transporter genes in small pulmonary arteries and pulmonary artery smooth muscle cells (PASMCs).

TRESK (K2P18.1) Background Potassium Channel Is Activated by Novel-Type Protein Kinase C via Dephosphorylation.

TRESK (K2P18.1) background K channel is a major determinant of the excitability of primary sensory neurons. It has been reported that human TRESK is activated by the protein kinase C (PKC) activator PMA (phorbol 12-myristate 13-acetate) in oocytes.

Chemically Modified Derivatives of the Activator Compound Cloxyquin Exert Inhibitory Effect on TRESK (K18.1) Background Potassium Channel.

Cloxyquin has been reported as a specific activator of TRESK [TWIK-related spinal cord K channel (also known as K18.1)] background potassium channel. In this study, we have synthetized chemically modified analogs of cloxyquin and tested their effects on TRESK and other K channels.

TRESK background potassium channel is not gated at the helix bundle crossing near the cytoplasmic end of the pore.

Two-pore domain K+ channels (K2P) are responsible for background K+ currents and regulate the resting membrane potential and cellular excitability. Their activity is controlled by a large variety of physicochemical factors and intracellular signaling pathways. The majority of these effects converge on the intracellular C-terminus of the channels, resulting in the modification of the gating at the selectivity filter.

Selective and state-dependent activation of TRESK (K 18.1) background potassium channel by cloxyquin.

Background And Purpose: Cloxyquin (5-cloroquinolin-8-ol) has been described as an activator of TRESK (K 18.1, TWIK-related spinal cord K channel) background potassium channel. We have examined the specificity of the drug by testing several K channels.

Formation of Functional Heterodimers by TREK-1 and TREK-2 Two-pore Domain Potassium Channel Subunits.

Two-pore domain (K2P) potassium channels are the major molecular correlates of the background (leak) K(+) current in a wide variety of cell types. They generally play a key role in setting the resting membrane potential and regulate the response of excitable cells to various stimuli. K2P channels usually function as homodimers, and only a few examples of heteromerization have been previously reported.