<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension"^^ . "Background and purpose\r\nPulmonary arterial hypertension (PAH) is a progressive disease in which chronic membrane potential (Em) depolarisation of the pulmonary arterial smooth muscle cells (PASMCs) causes calcium overload, a key pathological alteration. Under resting conditions, the negative Em is mainly set by two pore domain potassium (K2P) channels, of which the TASK-1 has been extensively investigated.\r\n\r\nExperimental Approach\r\nIon channel currents and membrane potential of primary cultured human(h) PASMCs were measured using the voltage- and current clamp methods. Intracellular [Ca2+] was monitored using fluorescent microscopy. Pulmonary BP and vascular tone measurements were also performed ex vivo using a rat PAH model.\r\n\r\nKey Results\r\nTREK-1 was the most abundantly expressed K2P in hPASMCs of healthy donors and idiopathic(I) PAH patients. Background K+-current was similar in hPASMCs for both groups and significantly enhanced by the TREK activator ML-335. In donor hPASMCs, siRNA silencing or pharmacological inhibition of TREK-1 caused depolarisation, reminiscent of the electrophysiological phenotype of idiopathic PAH. ML-335 hyperpolarised donor hPASMCs and normalised the Em of IPAH hPASMCs. A close link was found between TREK-1 activity and intracellular Ca2+-signalling using a channel activator, ML-335, and an inhibitor, spadin. In the rat, ML-335 relaxed isolated pre-constricted pulmonary arteries and significantly decreased pulmonary arterial pressure in the isolated perfused lung.\r\n\r\nConclusions and Implications\r\nThese data suggest that TREK-1is a key factor in Em setting and Ca2+ homeostasis of hPASMC, and therefore, essential for maintenance of a low resting pulmonary vascular tone. Thus TREK-1 may represent a new therapeutic target for PAH."^^ . "2024" . . . "181" . "19" . . "BRITISH JOURNAL OF PHARMACOLOGY"^^ . . . "00071188" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "Miklós"^^ . "Lengyel"^^ . "Miklós Lengyel"^^ . . "Dusan"^^ . "Jeremic"^^ . "Dusan Jeremic"^^ . . "Andrea"^^ . "Olschewski"^^ . "Andrea Olschewski"^^ . . "János"^^ . "Almássy"^^ . "János Almássy"^^ . . "Alice"^^ . "Dobolyi"^^ . "Alice Dobolyi"^^ . . "Konrad"^^ . "Hoetzenecker"^^ . "Konrad Hoetzenecker"^^ . . "Péter"^^ . "Enyedi"^^ . "Péter Enyedi"^^ . . "Horst"^^ . "Olschewski"^^ . "Horst Olschewski"^^ . . "Réka"^^ . "Csáki"^^ . "Réka Csáki"^^ . . "Chandran"^^ . "Nagaraj"^^ . "Chandran Nagaraj"^^ . . "Mohammad Ali"^^ . "Khozeimeh"^^ . "Mohammad Ali Khozeimeh"^^ . . "Élettani Intézet SE / AOK / I ÉI [2000-]"^^ . . . . . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Text)"^^ . . . . . . "BritishJPharmacology-2024-Csaki-TheTREK1potassiumchannelisapotentialpharmacologicaltargetfor1.pdf"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "small.jpg"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Text)"^^ . . . . . "bph16426-toc-0001-m.jpg"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #225005 \n\nThe TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension\n\n" . "text/html" . . . "R1 Medicine (General) / orvostudomány általában"@en . .