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

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 build new pharmacological tools for the modulation of this channel.

journal_name

J Cell Physiol

authors

Canella R,Martini M,Cavicchio C,Cervellati F,Benedusi M,Valacchi G

doi

10.1002/jcp.28396

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

17704-17713

issue

10

eissn

0021-9541

issn

1097-4652

journal_volume

234

pub_type

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