Potassium channels in alveolar epithelium cells: the particular case of the channel TREK-1

Potassium is considered the ion mainly responsible for maintaining the driving force acting on the ionic and solvent flow through the cell membrane. This study concerns K+ channels in the alveolar cells and in particular the study of TREK-1, a K+ channel activated by swelling and other disturbing factors. Under conditions of resting membrane potential, the most relevant membrane currents in alveolar cells are the potassium (IK) and chloride (ICl) ones. In order to isolate IK we inhibited chloride flow by two specific inhibitors: 9-AC and DCPIB, the most specific inhibitor of the ORCC channels. Surprisingly an increase in total membrane current was observed with 9-AC, with DCPIB, and with both drugs treatment at the same time. We excluded the direct involvement of Cl- ions in the modulation of the IK by silencing ORCC and retesting the two drugs. Trying to identify the involved K+ channel, we found that other studies indicated TREK-1 as a target of DCPIB. Through immunocytochemical techniques we demonstrated the presence of TREK-1 in alveolar cells and by patch clamp experiments with a specific inhibitor for TREK-1 (BaCl2), we verified that TREK-1 is actually the target of the two drugs. Since the activity of the TREK-1 channel 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.