Involvement of the TREK-1 channel in human alveolar cell membrane potential and its regulation by inhibitors of the chloride current

Journal of Cellular Physiology
Rita CanellaGiuseppe Valacchi

Abstract

K+ channels of the alveolar epithelium control the driving force acting on the ionic and solvent flow through the cell membrane contributing to the maintenance of cell volume and the constitution of epithelial lining fluid. In the present work, we analyze the effect of the Cl- channel inhibitors: (4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-inden-5-yl)oxy] butanoic acid (DCPIB) and 9-anthracenecarboxylic acid (9-AC) on the total current in a type II pneumocytes (A549 cell line) model by patch clamp, immunocytochemical, and gene knockdown techniques. We noted that DCPIB and 9-AC promote the activation of K conductance. In fact, they significantly increase the intensity of the current and shift its reversal potential to values more negative than the control. By silencing outward rectifier channel in its anoctamin 6 portion, we excluded a direct involvement of Cl- ions in modulation of IK and, by means of functional tests with its specific inhibitor spadin, we identified the TREK-1 channel as the presumable target of both drugs. As the activity of TREK-1 has a key role for the correct functioning of the alveolar epithelium, the identification of DCPIB and 9-AC molecules as its activators suggests their possible use to...Continue Reading

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Citations

Dec 16, 2020·Scientific Reports·Tatiana ZyrianovaAndreas Schwingshackl
Aug 28, 2021·International Journal of Molecular Sciences·Miklós LengyelGábor Czirják

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