Objectives: 

The pulmonary epithelium is permanently exposed to mechanical forces (e.g. shear force and stretch). In an earlier study using freshly isolated lung preparations of Xenopus laevis it was indicated that stretch leads to an activation of ATP-sensitive K+ (KATP) channels (Bogdan et al. 2008). The aim of the present study was to further clarify the mechanosensitive KATP channel activation mechanism.

Materials: 

Methods: A modified Ussing-chamber that enabled the application of hydrostatic pressure (HP) was used to mechanically stimulate the native pulmonary epithelium of Xenopus while the short-circuit current (ISC) was recorded. To clarify the mechanosensitive activation of KATP channels the specific inhibitor HMR1098 was used. To test the contribution of hemichannels in this process specific connexin (meclofenamic-acid) and pannexin (probenecid) hemichannel inhibitors were applied. Further samples of the out flowing perfusate were collected for the determination of extracellular ATP levels via a luminescence ATP detection assay.

Results: 

Under control conditions increased HP led to a decrease of the ISC (17.6 ± 2%, P<0.001). The KATP channel inhibitors glibenclamide and HMR1098 prevented the HP induced current decrease. Interestingly the HP induced current decrease was also reversed by specific connexin and pannexin hemichannel inhibitors. Further under control conditions the pressure induced effect was accompanied by an increased release of ATP. Interestingly HP induced ATP release was inhibited by connexin and pannexin hemichannel inhibitors.

Conclusions: 

Since different hemichannel inhibitors inhibited the HP induced KATP channel activation and the ATP release, we hypothesize a novel mechanotransduction process in native pulmonary epithelium with a KATP channel activation induced by intracellular ATP-release via mechanosensitive connexin and pannexin hemichannels. This process might be responsible to mediate ion and fluid reabsorption under native, dynamic conditions.