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Involvement of the TREK‐1 channel in human alveolar cell membrane potential and its regulation by inhibitors of the chloride current
Author(s) -
Canella Rita,
Martini Marta,
Cavicchio Carlotta,
Cervellati Franco,
Benedusi Mascia,
Valacchi Giuseppe
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28396
Subject(s) - chloride channel , alveolar epithelium , chemistry , patch clamp , biophysics , epithelium , ion channel , membrane potential , ion transporter , microbiology and biotechnology , cell culture , membrane , biochemistry , biology , pathology , medicine , genetics , receptor
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 I K 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 build new pharmacological tools for the modulation of this channel.